chrX-50634194-G-T

Position:

• chrX-50634194-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020717.5(SHROOM4):​c.1879C>A​(p.Pro627Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,074 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: SHROOM4 NM_020717.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523

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]

SHROOM4 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12189248).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM4	NM_020717.5	c.1879C>A	p.Pro627Thr	missense_variant	4/9	ENST00000376020.9	NP_065768.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHROOM4	ENST00000376020.9	c.1879C>A	p.Pro627Thr	missense_variant	4/9	2	NM_020717.5	ENSP00000365188.2
SHROOM4	ENST00000289292.11	c.1879C>A	p.Pro627Thr	missense_variant	4/10	1		ENSP00000289292.7
SHROOM4	ENST00000460112.3	c.1531C>A	p.Pro511Thr	missense_variant	3/8	5		ENSP00000421450.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.00000546 AC: 1 AN: 183309 Hom.: 0 AF XY: 0.0000148 AC XY: 1 AN XY: 67773

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

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: 9.11e-7 AC: 1 AN: 1098074 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 1 AN XY: 363450

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.51
DEOGEN2	Benign	0.0077	T;T;.
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.66	T;.;T
M_CAP	Pathogenic	0.60	D
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.0	L;L;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.13
Sift	Uncertain	0.010	D;D;D
Sift4G	Benign	0.83	T;T;T
Polyphen		0.0040	B;B;.
Vest4		0.025
MutPred		0.17		Loss of catalytic residue at P626 (P = 0.0185);Loss of catalytic residue at P626 (P = 0.0185);.;
MVP		0.51
MPC		0.22
ClinPred		0.054	T
GERP RS		4.2
Varity_R		0.14
gMVP		0.16

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

Other links and lift over

dbSNP: rs150861758; hg19: chrX-50377194;