chrX-50598377-C-G

Variant names:

• chrX-50598377-C-G
• NM_020717.5:c.4101G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020717.5(SHROOM4):​c.4101G>C​(p.Leu1367Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,097,684 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: SHROOM4 NM_020717.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3455897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHROOM4	NM_020717.5	c.4101G>C	p.Leu1367Phe	missense_variant	Exon 8 of 9	ENST00000376020.9	NP_065768.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHROOM4	ENST00000376020.9	c.4101G>C	p.Leu1367Phe	missense_variant	Exon 8 of 9	2	NM_020717.5	ENSP00000365188.2
SHROOM4	ENST00000289292.11	c.4101G>C	p.Leu1367Phe	missense_variant	Exon 8 of 10	1		ENSP00000289292.7
SHROOM4	ENST00000460112.3	c.3753G>C	p.Leu1251Phe	missense_variant	Exon 7 of 8	5		ENSP00000421450.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097684 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 1 AN XY: 363058

Gnomad4 AFR exome AF: 0.0000379

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: 0.00

Gnomad4 OTH exome AF: 0.0000217

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	T;T;.
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.97	D;.;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.3	M;M;.
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.039	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.27
MutPred		0.60		Gain of catalytic residue at L1367 (P = 0.0738);Gain of catalytic residue at L1367 (P = 0.0738);.;
MVP		0.35
MPC		0.55
ClinPred		0.93	D
GERP RS		3.5
Varity_R		0.32
gMVP		0.19

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-50341377;