X-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/exons MANE Protein UniProt
SHROOM2NM_001649.4 linkc.222C>T p.Ile74Ile synonymous_variant 2/10 ENST00000380913.8 NP_001640.1 Q13796
SHROOM2XM_005274500.5 linkc.222C>T p.Ile74Ile synonymous_variant 2/10 XP_005274557.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SHROOM2ENST00000380913.8 linkc.222C>T p.Ile74Ile synonymous_variant 2/101 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
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesApr 15, 2019This 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