X-50596721-G-C

Position:

• chrX-50596721-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020717.5(SHROOM4):​c.4456C>G​(p.Leu1486Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: SHROOM4 NM_020717.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.22

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.761

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHROOM4	NM_020717.5	c.4456C>G	p.Leu1486Val	missense_variant	9/9	ENST00000376020.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHROOM4	ENST00000376020.9	c.4456C>G	p.Leu1486Val	missense_variant	9/9	2	NM_020717.5	P1
SHROOM4	ENST00000289292.11	c.4456C>G	p.Leu1486Val	missense_variant	9/10	1		P1
SHROOM4	ENST00000460112.3	c.4108C>G	p.Leu1370Val	missense_variant	8/8	5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Clinical Genetics Laboratory, Skane University Hospital Lund

May 27, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.077	T;T;.
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.75	T;.;T
M_CAP	Uncertain	0.26	D
MetaRNN	Pathogenic	0.76	D;D;D
MetaSVM	Benign	-0.34	T
MutationAssessor	Pathogenic	2.9	M;M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Uncertain	0.44
Sift	Uncertain	0.0010	D;D;D
Sift4G	Benign	0.14	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.56
MutPred		0.76		Loss of stability (P = 0.0568);Loss of stability (P = 0.0568);.;
MVP		0.81
MPC		0.53
ClinPred		0.98	D
GERP RS		6.0
Varity_R		0.62
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-50339721;