NM_020717.5:c.3411_3413dupGGA

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_020717.5(SHROOM4):c.3411_3413dupGGA(p.Glu1138dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,091,571 control chromosomes in the GnomAD database, including 29,069 homozygotes. There are 71,921 hemizygotes in GnomAD. 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 0.27 ( 3319 hom., 6730 hem., cov: 14)

Exomes 𝑓: 0.28 ( 25750 hom. 65191 hem. )

Consequence

SHROOM4
NM_020717.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.350

Publications

9 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 -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_020717.5

BP6

Variant X-50607728-T-TTCC is Benign according to our data. Variant chrX-50607728-T-TTCC is described in ClinVar as Benign. ClinVar VariationId is 95971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHROOM4	NM_020717.5 link	c.3411_3413dupGGA	p.Glu1138dup	disruptive_inframe_insertion	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.3411_3413dupGGA	p.Glu1138dup	disruptive_inframe_insertion	Exon 6 of 9	2	NM_020717.5	ENSP00000365188.2	Q9ULL8-1
SHROOM4	ENST00000289292.11 link	c.3411_3413dupGGA	p.Glu1138dup	disruptive_inframe_insertion	Exon 6 of 10	1		ENSP00000289292.7	Q9ULL8-1
SHROOM4	ENST00000460112.3 link	c.3063_3065dupGGA	p.Glu1022dup	disruptive_inframe_insertion	Exon 5 of 8	5		ENSP00000421450.1	Q9ULL8-2

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

28804

AN:

105509

Hom.:

3329

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.245

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.313

Gnomad EAS

AF:

0.230

Gnomad SAS

AF:

0.360

Gnomad FIN

AF:

0.201

Gnomad MID

AF:

0.353

Gnomad NFE

AF:

0.329

Gnomad OTH

AF:

0.293

GnomAD2 exomes

AF:

0.212

AC:

26912

AN:

127114

AF XY:

0.103

show subpopulations

Gnomad AFR exome

AF:

0.152

Gnomad AMR exome

AF:

0.126

Gnomad ASJ exome

AF:

0.254

Gnomad EAS exome

AF:

0.183

Gnomad FIN exome

AF:

0.204

Gnomad NFE exome

AF:

0.245

Gnomad OTH exome

AF:

0.240

GnomAD4 exome

AF:

0.283

AC:

278624

AN:

986025

Hom.:

25750

Cov.:

AF XY:

0.229

AC XY:

65191

AN XY:

284763

show subpopulations

African (AFR)

AF:

0.175

AC:

4208

AN:

24071

American (AMR)

AF:

0.141

AC:

4600

AN:

32539

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

4937

AN:

17318

East Asian (EAS)

AF:

0.224

AC:

6401

AN:

28615

South Asian (SAS)

AF:

0.342

AC:

14903

AN:

43531

European-Finnish (FIN)

AF:

0.238

AC:

9043

AN:

38021

Middle Eastern (MID)

AF:

0.301

AC:

1076

AN:

3578

European-Non Finnish (NFE)

AF:

0.293

AC:

221503

AN:

756492

Other (OTH)

AF:

0.286

AC:

11953

AN:

41860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

8067

16134

24202

32269

40336

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7756

15512

23268

31024

38780

<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:

0.273

AC:

28779

AN:

105546

Hom.:

3319

Cov.:

AF XY:

0.235

AC XY:

6730

AN XY:

28652

show subpopulations

African (AFR)

AF:

0.197

AC:

5577

AN:

28371

American (AMR)

AF:

0.221

AC:

2189

AN:

9919

Ashkenazi Jewish (ASJ)

AF:

0.313

AC:

803

AN:

2563

East Asian (EAS)

AF:

0.229

AC:

767

AN:

3347

South Asian (SAS)

AF:

0.357

AC:

804

AN:

2250

European-Finnish (FIN)

AF:

0.201

AC:

1087

AN:

5410

Middle Eastern (MID)

AF:

0.360

AC:

AN:

211

European-Non Finnish (NFE)

AF:

0.329

AC:

16906

AN:

51409

Other (OTH)

AF:

0.290

AC:

409

AN:

1410

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

740

1481

2221

2962

3702

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

290

580

870

1160

1450

<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:

0.171

Hom.:

966

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Dec 29, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 19, 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:no assertion criteria provided

Collection Method:clinical testing

- -

X-linked intellectual disability, Stocco dos Santos type

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.35

Mutation Taster

=84/16

polymorphism (auto)

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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