X-100644247-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014467.3(SRPX2):c.-399G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 111,205 control chromosomes in the GnomAD database, including 940 homozygotes. There are 4,528 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (940 hom., 4525 hem., cov: 22)
  • Exomes 𝑓: 0.16 (0 hom. 3 hem.)
• Consequence: SRPX2 NM_014467.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.444

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant X-100644247-G-C is Benign according to our data. Variant chrX-100644247-G-C is described in ClinVar as [Benign]. Clinvar id is 1260803.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRPX2	NM_014467.3	c.-399G>C		5_prime_UTR_variant	1/11	ENST00000373004.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRPX2	ENST00000373004.5	c.-399G>C		5_prime_UTR_variant	1/11	1	NM_014467.3	P1
SRPX2	ENST00000640889.1	c.-270G>C		5_prime_UTR_variant	1/7	5
SRPX2	ENST00000481988.1	n.27G>C		non_coding_transcript_exon_variant	1/3	3
SRPX2	ENST00000640020.1	n.49G>C		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes AF: 0.143 AC: 15898 AN: 111127 Hom.: 939 Cov.: 22 AF XY: 0.135 AC XY: 4497 AN XY: 33379

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.0556

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.0347

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.160 AC: 4 AN: 25 Hom.: 0 Cov.: 0 AF XY: 0.200 AC XY: 3 AN XY: 15

Gnomad4 AFR exome AF: 1.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.143 AC: 15928 AN: 111180 Hom.: 940 Cov.: 22 AF XY: 0.135 AC XY: 4525 AN XY: 33442

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.0347

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.156

Alfa AF: 0.122 Hom.: 678

Bravo AF: 0.151

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 10, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	4.6
Dann	Benign	0.88

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: rs1343213; hg19: chrX-99899244;