chrX-50596895-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_020717.5(SHROOM4):c.4282G>A(p.Val1428Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000455 in 1,210,061 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 20 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., 3 hem., cov: 24)

Exomes 𝑓: 0.000045 ( 0 hom. 17 hem. )

Consequence

SHROOM4
NM_020717.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0840

Publications

0 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):

congenital anomaly of kidney and urinary tract
Inheritance: XL Classification: STRONG Submitted by: PanelApp Australia
idiopathic generalized epilepsy
Inheritance: XL Classification: STRONG Submitted by: PanelApp Australia
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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.065712065).

BS2

High Hemizygotes in GnomAd4 at 3 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020717.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SHROOM4	NM_020717.5	MANE Select	c.4282G>A	p.Val1428Met	missense	Exon 9 of 9	NP_065768.2	Q9ULL8-1
SHROOM4	NR_027121.3		n.4458G>A		non_coding_transcript_exon	Exon 9 of 10
SHROOM4	NR_172068.1		n.4323G>A		non_coding_transcript_exon	Exon 8 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SHROOM4	ENST00000376020.9	TSL:2 MANE Select	c.4282G>A	p.Val1428Met	missense	Exon 9 of 9	ENSP00000365188.2	Q9ULL8-1
SHROOM4	ENST00000289292.11	TSL:1	c.4282G>A	p.Val1428Met	missense	Exon 9 of 10	ENSP00000289292.7	Q9ULL8-1
SHROOM4	ENST00000898514.1		c.4147G>A	p.Val1383Met	missense	Exon 8 of 8	ENSP00000568573.1

Frequencies

GnomAD3 genomes

AF:

0.0000533

AC:

AN:

112482

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000935

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000938

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000166

AC:

AN:

180999

AF XY:

0.0000152

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000372

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000446

AC:

AN:

1097579

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

362959

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26393

American (AMR)

AF:

0.00

AC:

AN:

35177

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19363

East Asian (EAS)

AF:

0.00

AC:

AN:

30197

South Asian (SAS)

AF:

0.00

AC:

AN:

53912

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40458

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4107

European-Non Finnish (NFE)

AF:

0.0000546

AC:

AN:

841901

Other (OTH)

AF:

0.0000434

AC:

AN:

46071

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0000533

AC:

AN:

112482

Hom.:

Cov.:

AF XY:

0.0000866

AC XY:

AN XY:

34636

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30919

American (AMR)

AF:

0.0000935

AC:

AN:

10696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

3550

South Asian (SAS)

AF:

0.00

AC:

AN:

2701

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6208

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000938

AC:

AN:

53320

Other (OTH)

AF:

0.00

AC:

AN:

1507

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Hom

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.0000494

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.011

FATHMM_MKL

Benign

0.23

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.011

MetaRNN

Benign

0.066

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

PhyloP100

0.084

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.44

REVEL

Benign

0.044

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0060

Polyphen

0.80

Vest4

0.14

MutPred

0.43

Gain of disorder (P = 0.0648)

MVP

0.25

MPC

0.16

ClinPred

0.13

GERP RS

2.3

Varity_R

0.19

gMVP

0.29

Mutation Taster

=99/1

polymorphism

(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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over