X-9873674-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP3BS2_Supporting

The NM_001649.4(SHROOM2):​c.188C>T​(p.Ala63Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000132 in 1,210,001 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.000014 ( 0 hom. 2 hem. )

Consequence

SHROOM2
NM_001649.4 missense

Scores

3
8
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.42
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.815
BS2
High Hemizygotes in GnomAdExome4 at 2 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.188C>T p.Ala63Val missense_variant 2/10 ENST00000380913.8 NP_001640.1 Q13796
SHROOM2XM_005274500.5 linkc.188C>T p.Ala63Val missense_variant 2/10 XP_005274557.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SHROOM2ENST00000380913.8 linkc.188C>T p.Ala63Val missense_variant 2/101 NM_001649.4 ENSP00000370299.3 Q13796

Frequencies

GnomAD3 genomes
AF:
0.00000891
AC:
1
AN:
112187
Hom.:
0
Cov.:
23
AF XY:
0.0000291
AC XY:
1
AN XY:
34361
show subpopulations
Gnomad AFR
AF:
0.0000324
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000109
AC:
2
AN:
183110
Hom.:
0
AF XY:
0.0000148
AC XY:
1
AN XY:
67562
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:
0.00
Gnomad FIN exome
AF:
0.0000625
Gnomad NFE exome
AF:
0.0000122
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
15
AN:
1097759
Hom.:
0
Cov.:
30
AF XY:
0.00000551
AC XY:
2
AN XY:
363129
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000284
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000166
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000891
AC:
1
AN:
112242
Hom.:
0
Cov.:
23
AF XY:
0.0000290
AC XY:
1
AN XY:
34426
show subpopulations
Gnomad4 AFR
AF:
0.0000323
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 06, 2021The c.188C>T (p.A63V) alteration is located in exon 2 (coding exon 2) of the SHROOM2 gene. This alteration results from a C to T substitution at nucleotide position 188, causing the alanine (A) at amino acid position 63 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.49
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
23
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.13
T
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.93
D
M_CAP
Pathogenic
0.42
D
MetaRNN
Pathogenic
0.82
D
MetaSVM
Benign
-0.39
T
MutationAssessor
Uncertain
2.7
M
PrimateAI
Uncertain
0.69
T
PROVEAN
Uncertain
-2.8
D
REVEL
Uncertain
0.35
Sift
Uncertain
0.0030
D
Sift4G
Benign
0.14
T
Polyphen
1.0
D
Vest4
0.58
MVP
0.51
MPC
0.41
ClinPred
0.81
D
GERP RS
5.2
Varity_R
0.51
gMVP
0.46

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: rs201114383; hg19: chrX-9841714; API