Variant rs540437538 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_020717.5(SHROOM4):c.2896-17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00045 in 1,193,028 control chromosomes in the GnomAD database, including 1 homozygotes. There are 292 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.00047 ( 1 hom. 286 hem. )

Consequence

SHROOM4
NM_020717.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.212

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 links:

SHROOM4 (HGNC:):

SHROOM4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant X-50627692-T-C is Benign according to our data. Variant chrX-50627692-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 212179.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM4	NM_020717.5 linkuse as main transcript	c.2896-17A>G		intron_variant		ENST00000376020.9	NP_065768.2	Q9ULL8-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
SHROOM4	ENST00000376020.9 linkuse as main transcript	c.2896-17A>G	intron_variant	2	NM_020717.5	ENSP00000365188.2	Q9ULL8-1
SHROOM4	ENST00000289292.11 linkuse as main transcript	c.2896-17A>G	intron_variant	1		ENSP00000289292.7	Q9ULL8-1
SHROOM4	ENST00000460112.3 linkuse as main transcript	c.2548-17A>G	intron_variant	5		ENSP00000421450.1	Q9ULL8-2

Frequencies

GnomAD3 genomes

AF:

0.000242

AC:

AN:

111783

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

AN XY:

33955

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00949

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.000665

GnomAD3 exomes

AF:

0.000908

AC:

165

AN:

181681

Hom.:

AF XY:

0.00113

AC XY:

AN XY:

66251

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 SAS exome

AF:

0.00877

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000472

AC:

510

AN:

1081191

Hom.:

Cov.:

AF XY:

0.000823

AC XY:

286

AN XY:

347301

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000568

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00880

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000847

Gnomad4 OTH exome

AF:

0.000637

GnomAD4 genome

AF:

0.000241

AC:

AN:

111837

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

AN XY:

34019

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00952

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.000657

Bravo

AF:

0.0000680

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jun 11, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.89

DANN

Benign

0.59

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over