rs6614552

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020717.5(SHROOM4):c.3414A>G(p.Glu1138Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,112,932 control chromosomes in the GnomAD database, including 1,063 homozygotes. There are 2,868 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. E1138dup) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.064 ( 609 hom., 1315 hem., cov: 19)

Exomes 𝑓: 0.0078 ( 454 hom. 1553 hem. )

Consequence

SHROOM4
NM_020717.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.38

Publications

6 publications found

Variant links:

Genes affected

SHROOM4 (HGNC:29215): (shroom family member 4) This gene encodes a member of the APX/Shroom family, which contain an N-terminal PDZ domain and a C-terminal ASD2 motif. The encoded protein may play a role in cytoskeletal architecture. Mutations in this gene have been linked to the X-linked Stocco dos Santos syndrome characterized by cognitive disabilities. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2017]

SHROOM4 Gene-Disease associations (from GenCC):

X-linked intellectual disability, Stocco dos Santos type
Inheritance: XL Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
complex neurodevelopmental disorder
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics
X-linked complex neurodevelopmental disorder
Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

SHROOM4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.09).

BP6

Variant X-50607728-T-C is Benign according to our data. Variant chrX-50607728-T-C is described in ClinVar as Benign. ClinVar VariationId is 95972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHROOM4	NM_020717.5 link	c.3414A>G	p.Glu1138Glu	synonymous_variant	Exon 6 of 9	ENST00000376020.9	NP_065768.2	Q9ULL8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SHROOM4	ENST00000376020.9 link	c.3414A>G	p.Glu1138Glu	synonymous_variant	Exon 6 of 9	2	NM_020717.5	ENSP00000365188.2	Q9ULL8-1
SHROOM4	ENST00000289292.11 link	c.3414A>G	p.Glu1138Glu	synonymous_variant	Exon 6 of 10	1		ENSP00000289292.7	Q9ULL8-1
SHROOM4	ENST00000460112.3 link	c.3066A>G	p.Glu1022Glu	synonymous_variant	Exon 5 of 8	5		ENSP00000421450.1	Q9ULL8-2

Frequencies

GnomAD3 genomes

AF:

0.0637

AC:

6724

AN:

105625

Hom.:

605

Cov.:

show subpopulations

Gnomad AFR

AF:

0.222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0262

Gnomad ASJ

AF:

0.0113

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000884

Gnomad FIN

AF:

0.000184

Gnomad MID

AF:

0.0217

Gnomad NFE

AF:

0.00163

Gnomad OTH

AF:

0.0494

GnomAD2 exomes

AF:

0.0189

AC:

2404

AN:

127114

AF XY:

0.0125

show subpopulations

Gnomad AFR exome

AF:

0.215

Gnomad AMR exome

AF:

0.0121

Gnomad ASJ exome

AF:

0.0129

Gnomad EAS exome

AF:

0.000186

Gnomad FIN exome

AF:

0.000829

Gnomad NFE exome

AF:

0.00152

Gnomad OTH exome

AF:

0.0133

GnomAD4 exome

AF:

0.00777

AC:

7827

AN:

1007271

Hom.:

454

Cov.:

AF XY:

0.00514

AC XY:

1553

AN XY:

302339

show subpopulations

African (AFR)

AF:

0.227

AC:

5447

AN:

23974

American (AMR)

AF:

0.0126

AC:

415

AN:

32872

Ashkenazi Jewish (ASJ)

AF:

0.0117

AC:

206

AN:

17629

East Asian (EAS)

AF:

0.000103

AC:

AN:

29054

South Asian (SAS)

AF:

0.00120

AC:

AN:

45941

European-Finnish (FIN)

AF:

0.000545

AC:

AN:

38563

Middle Eastern (MID)

AF:

0.0216

AC:

AN:

3663

European-Non Finnish (NFE)

AF:

0.000990

AC:

765

AN:

772932

Other (OTH)

AF:

0.0196

AC:

836

AN:

42643

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

256

512

767

1023

1279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

344

516

688

860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0639

AC:

6753

AN:

105661

Hom.:

609

Cov.:

AF XY:

0.0458

AC XY:

1315

AN XY:

28733

show subpopulations

African (AFR)

AF:

0.222

AC:

6303

AN:

28364

American (AMR)

AF:

0.0263

AC:

261

AN:

9935

Ashkenazi Jewish (ASJ)

AF:

0.0113

AC:

AN:

2565

East Asian (EAS)

AF:

0.00

AC:

AN:

3358

South Asian (SAS)

AF:

0.000887

AC:

AN:

2256

European-Finnish (FIN)

AF:

0.000184

AC:

AN:

5426

Middle Eastern (MID)

AF:

0.0191

AC:

AN:

209

European-Non Finnish (NFE)

AF:

0.00163

AC:

AN:

51478

Other (OTH)

AF:

0.0488

AC:

AN:

1413

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

200

400

599

799

999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0367

Hom.:

257

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jul 12, 2015

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Oct 11, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 25, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

SHROOM4-related disorder

Benign:1

Jun 11, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.25

(source)

DANN

Benign

0.42

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over