rs797045961

Variant names:

• chrX-50695810-C-G
• NM_020717.5:c.245G>C

Your query was ambiguous. Multiple possible variants found:

• chrX-50695810-C-G
• chrX-50695810-C-T

Variant summary

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

The NM_020717.5(SHROOM4):​c.245G>C​(p.Arg82Pro) 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 1,098,091 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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. 0 hem.)
• Consequence: SHROOM4 NM_020717.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.02

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHROOM4	NM_020717.5	c.245G>C	p.Arg82Pro	missense_variant	Exon 2 of 9	ENST00000376020.9	NP_065768.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHROOM4	ENST00000376020.9	c.245G>C	p.Arg82Pro	missense_variant	Exon 2 of 9	2	NM_020717.5	ENSP00000365188.2
SHROOM4	ENST00000289292.11	c.245G>C	p.Arg82Pro	missense_variant	Exon 2 of 10	1		ENSP00000289292.7
SHROOM4	ENST00000484922.1	n.128G>C		non_coding_transcript_exon_variant	Exon 1 of 2	5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098091 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363469

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000119

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	Pathogenic	0.99
BayesDel_addAF	Benign	-0.0080	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.077	T;T
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.88	D;.
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.50	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		1.0	D;D
Vest4		0.53
MutPred		0.59		Loss of MoRF binding (P = 0.0016);Loss of MoRF binding (P = 0.0016);
MVP		0.29
MPC		0.63
ClinPred		0.98	D
GERP RS		5.4
Varity_R		0.82
gMVP		0.85

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-50438810;