rs1343213

Variant names:

• chrX-100644247-G-C
• rs1343213
• NM_014467.3:c.-399G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014467.3(SRPX2):​c.-399G>C variant causes a 5 prime UTR premature start codon gain 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_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.444
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• rolandic epilepsy-speech dyspraxia syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• polymicrogyria, bilateral perisylvian, X-linked

  Inheritance: XL Classification: LIMITED Submitted by: G2P
• rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked

  Inheritance: XL Classification: LIMITED, NO_KNOWN Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• epilepsy

  Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1260803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014467.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRPX2	NM_014467.3	MANE Select	c.-399G>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_055282.1	O60687
	SRPX2	NM_014467.3	MANE Select	c.-399G>C		5_prime_UTR	Exon 1 of 11	NP_055282.1	O60687

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRPX2	ENST00000373004.5	TSL:1 MANE Select	c.-399G>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000362095.3	O60687
	SRPX2	ENST00000373004.5	TSL:1 MANE Select	c.-399G>C		5_prime_UTR	Exon 1 of 11	ENSP00000362095.3	O60687
	SRPX2	ENST00000640889.1	TSL:5	c.-270G>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000492571.1	A0A1W2PRB1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 15898 AN: 111127 Hom.: 939 Cov.: 22

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

African (AFR) AF: 1.00 AC: 1 AN: 1

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.143 AC: 3 AN: 21

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.207 AC: 6331 AN: 30524

American (AMR) AF: 0.118 AC: 1232 AN: 10453

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 336 AN: 2645

East Asian (EAS) AF: 0.212 AC: 745 AN: 3510

South Asian (SAS) AF: 0.312 AC: 799 AN: 2564

European-Finnish (FIN) AF: 0.0347 AC: 209 AN: 6024

Middle Eastern (MID) AF: 0.143 AC: 31 AN: 217

European-Non Finnish (NFE) AF: 0.113 AC: 5972 AN: 53049

Other (OTH) AF: 0.156 AC: 235 AN: 1511

Alfa AF: 0.122 Hom.: 678

Bravo AF: 0.151

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.6
DANN	Benign	0.88
PhyloP100		-0.44
PromoterAI		0.0064	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1343213; hg19: chrX-99899244;