X-100665569-C-G

Position:

• chrX-100665569-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014467.3(SRPX2):​c.693C>G​(p.His231Gln) 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 1,098,192 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: SRPX2 NM_014467.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.61

Genes affected

SRPX2 (HGNC:30668): (sushi repeat containing protein X-linked 2) This gene encodes a secreted protein that contains three sushi repeat motifs. The encoded protein may play a role in the development of speech and language centers in the brain. This protein may also be involved in angiogenesis. Mutations in this gene are the cause of bilateral perisylvian polymicrogyria, rolandic epilepsy, speech dyspraxia and cognitive disability. [provided by RefSeq, May 2010]

SRPX2 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04529354).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRPX2	NM_014467.3	c.693C>G	p.His231Gln	missense_variant	7/11	ENST00000373004.5	NP_055282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRPX2	ENST00000373004.5	c.693C>G	p.His231Gln	missense_variant	7/11	1	NM_014467.3	ENSP00000362095.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.00000546 AC: 1 AN: 183066 Hom.: 0 AF XY: 0.0000148 AC XY: 1 AN XY: 67610

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: 1098192 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 1 AN XY: 363546

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	0.083
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.81
DEOGEN2	Benign	0.035	T;.
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.43	T;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.045	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.28	N;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.25	N;.
REVEL	Benign	0.035
Sift	Benign	0.29	T;.
Sift4G	Benign	0.22	T;.
Polyphen		0.0	B;.
Vest4		0.12
MutPred		0.63		Loss of glycosylation at S230 (P = 0.1011);.;
MVP		0.17
MPC		0.16
ClinPred		0.066	T
GERP RS		-4.4
Varity_R		0.059
gMVP		0.24

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: rs142719253; hg19: chrX-99920566;