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GeneBe

X-50596896-G-A

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.His1427=) 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

2

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.326 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Hemizygotes in GnomAd at 9 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SHROOM4NM_020717.5 linkuse as main transcriptc.4281C>T p.His1427= synonymous_variant 9/9 ENST00000376020.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SHROOM4ENST00000376020.9 linkuse as main transcriptc.4281C>T p.His1427= synonymous_variant 9/92 NM_020717.5 P1Q9ULL8-1
SHROOM4ENST00000289292.11 linkuse as main transcriptc.4281C>T p.His1427= synonymous_variant 9/101 P1Q9ULL8-1
SHROOM4ENST00000460112.3 linkuse as main transcriptc.3933C>T p.His1311= synonymous_variant 8/85 Q9ULL8-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000285
AC:
32
AN:
112387
Hom.:
0
Cov.:
24
AF XY:
0.000261
AC XY:
9
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:
38
AN:
181053
Hom.:
0
AF XY:
0.000228
AC XY:
15
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.:
2
Cov.:
31
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000285
AC:
32
AN:
112387
Hom.:
0
Cov.:
24
AF XY:
0.000261
AC XY:
9
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.:
2
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
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenOct 01, 2022SHROOM4: 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.

Other links and lift over

dbSNP: rs368241036; hg19: chrX-50339896; COSMIC: COSV56784681; COSMIC: COSV56784681; API