chrX-9786645-G-T

Variant names:

• chrX-9786645-G-T
• rs1335412484
• NM_001649.4:c.100G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001649.4(SHROOM2):​c.100G>T​(p.Gly34Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: SHROOM2 NM_001649.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.21
• Publications: 0 publications found

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]

ENSG00000310579 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001649.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHROOM2	NM_001649.4	MANE Select	c.100G>T	p.Gly34Cys	missense	Exon 1 of 10	NP_001640.1	Q13796

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHROOM2	ENST00000380913.8	TSL:1 MANE Select	c.100G>T	p.Gly34Cys	missense	Exon 1 of 10	ENSP00000370299.3	Q13796
	ENSG00000310579	ENST00000850985.1		c.100G>T	p.Gly34Cys	missense	Exon 1 of 10	ENSP00000521067.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 773917 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 236253

African (AFR) AF: 0.00 AC: 0 AN: 15973

American (AMR) AF: 0.00 AC: 0 AN: 4710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8324

East Asian (EAS) AF: 0.00 AC: 0 AN: 15340

South Asian (SAS) AF: 0.00 AC: 0 AN: 13768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14021

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 670232

Other (OTH) AF: 0.00 AC: 0 AN: 29791

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.81	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.52	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		4.2
PrimateAI	Pathogenic	0.94	D
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.32
MutPred		0.56		Loss of disorder (P = 0.056)
MVP		0.79
MPC		0.44
ClinPred		0.99	D
GERP RS		2.7
PromoterAI		-0.038	Neutral
Varity_R		0.72
gMVP		0.44
Mutation Taster		=57/43	polymorphism

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

Other links and lift over

dbSNP: rs1335412484; hg19: chrX-9754685;