chrX-9873708-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6BP7BS2_Supporting

The NM_001649.4(SHROOM2):​c.222C>T​(p.Ile74Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,209,780 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.000015 ( 0 hom. 8 hem. )

Consequence

SHROOM2
NM_001649.4 synonymous

Scores

2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.596
Variant links:
Genes affected
SHROOM2 (HGNC:630): (shroom family member 2) This gene represents the human homolog of Xenopus laevis apical protein (APX) gene, which is implicated in amiloride-sensitive sodium channel activity. It is expressed in endothelial cells and facilitates the formation of a contractile network within endothelial cells. Depletion of this gene results in an increase in endothelial sprouting, migration, and angiogenesis. This gene is highly expressed in the retina, and is a strong candidate for ocular albinism type 1 syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
Variant X-9873708-C-T is Benign according to our data. Variant chrX-9873708-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3060870.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-0.596 with no splicing effect.
BS2
High Hemizygotes in GnomAdExome4 at 8 geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SHROOM2NM_001649.4 linkc.222C>T p.Ile74Ile synonymous_variant Exon 2 of 10 ENST00000380913.8 NP_001640.1 Q13796
SHROOM2XM_005274500.5 linkc.222C>T p.Ile74Ile synonymous_variant Exon 2 of 10 XP_005274557.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SHROOM2ENST00000380913.8 linkc.222C>T p.Ile74Ile synonymous_variant Exon 2 of 10 1 NM_001649.4 ENSP00000370299.3 Q13796

Frequencies

GnomAD3 genomes
AF:
0.0000357
AC:
4
AN:
111958
Hom.:
0
Cov.:
23
AF XY:
0.0000293
AC XY:
1
AN XY:
34150
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000949
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000838
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000600
AC:
11
AN:
183381
Hom.:
0
AF XY:
0.0000737
AC XY:
5
AN XY:
67823
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000794
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000155
AC:
17
AN:
1097768
Hom.:
0
Cov.:
30
AF XY:
0.0000220
AC XY:
8
AN XY:
363126
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000497
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000434
GnomAD4 genome
AF:
0.0000357
AC:
4
AN:
112012
Hom.:
0
Cov.:
23
AF XY:
0.0000292
AC XY:
1
AN XY:
34214
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000948
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000841
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000340

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

SHROOM2-related disorder Benign:1
Apr 15, 2019
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.62
CADD
Benign
3.4
DANN
Benign
0.77

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: rs201837863; hg19: chrX-9841748; COSMIC: COSV66607898; COSMIC: COSV66607898; API