Variant rs368241036 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_020717.5(SHROOM4):c.4281C>T(p.His1427His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000823 in 1,209,976 control chromosomes in the GnomAD database, including 2 homozygotes. There are 327 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 0.00028 ( 0 hom., 9 hem., cov: 24)

Exomes 𝑓: 0.00088 ( 2 hom. 318 hem. )

Consequence

SHROOM4
NM_020717.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.326

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant X-50596896-G-A is Benign according to our data. Variant chrX-50596896-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1695299.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.326 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHROOM4	NM_020717.5 link	c.4281C>T	p.His1427His	synonymous_variant	Exon 9 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.4281C>T	p.His1427His	synonymous_variant	Exon 9 of 9	2	NM_020717.5	ENSP00000365188.2	Q9ULL8-1
SHROOM4	ENST00000289292.11 link	c.4281C>T	p.His1427His	synonymous_variant	Exon 9 of 10	1		ENSP00000289292.7	Q9ULL8-1
SHROOM4	ENST00000460112.3 link	c.3933C>T	p.His1311His	synonymous_variant	Exon 8 of 8	5		ENSP00000421450.1	Q9ULL8-2

Frequencies

GnomAD3 genomes

AF:

0.000285

AC:

AN:

112387

Hom.:

Cov.:

AF XY:

0.000261

AC XY:

AN XY:

34535

show subpopulations

Gnomad AFR

AF:

0.0000971

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000544

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000210

AC:

AN:

181053

Hom.:

AF XY:

0.000228

AC XY:

AN XY:

65679

show subpopulations

Gnomad AFR exome

AF:

0.0000767

Gnomad AMR exome

AF:

0.000110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000409

Gnomad OTH exome

AF:

0.000223

GnomAD4 exome

AF:

0.000878

AC:

964

AN:

1097589

Hom.:

Cov.:

AF XY:

0.000876

AC XY:

318

AN XY:

362963

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.000199

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00111

Gnomad4 OTH exome

AF:

0.000499

GnomAD4 genome

AF:

0.000285

AC:

AN:

112387

Hom.:

Cov.:

AF XY:

0.000261

AC XY:

AN XY:

34535

show subpopulations

Gnomad4 AFR

AF:

0.0000971

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000304

Hom.:

Bravo

AF:

0.000325

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SHROOM4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.21

DANN

Benign

0.62

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