rs146920180

Variant names:

• chrX-100667323-A-G
• rs146920180
• NM_014467.3:c.1011A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_014467.3(SRPX2):​c.1011A>G​(p.Gln337Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000339 in 1,208,773 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 15 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., 1 hem., cov: 24)
  • Exomes 𝑓: 0.000034 (0 hom. 14 hem.)
• Consequence: SRPX2 NM_014467.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.23
• Publications: 0 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant X-100667323-A-G is Benign according to our data. Variant chrX-100667323-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 583178.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.23 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 37 XL,AD gene.

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.1011A>G	p.Gln337Gln	synonymous	Exon 9 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.1011A>G	p.Gln337Gln	synonymous	Exon 9 of 11	ENSP00000362095.3	O60687
	SRPX2	ENST00000640282.1	TSL:5	c.57A>G	p.Gln19Gln	synonymous	Exon 2 of 3	ENSP00000491188.1	A0A1W2PNZ6
	SRPX2	ENST00000638920.1	TSL:5	n.1014A>G		non_coding_transcript_exon	Exon 8 of 10

Frequencies

GnomAD3 genomes AF: 0.0000358 AC: 4 AN: 111749 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000752

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000273 AC: 5 AN: 183466 AF XY: 0.0000442

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000610

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000337 AC: 37 AN: 1097024 Hom.: 0 Cov.: 31 AF XY: 0.0000386 AC XY: 14 AN XY: 362542

African (AFR) AF: 0.00 AC: 0 AN: 26367

American (AMR) AF: 0.00 AC: 0 AN: 35182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19341

East Asian (EAS) AF: 0.00 AC: 0 AN: 30151

South Asian (SAS) AF: 0.0000369 AC: 2 AN: 54131

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40428

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.0000404 AC: 34 AN: 841261

Other (OTH) AF: 0.0000217 AC: 1 AN: 46029

GnomAD4 genome AF: 0.0000358 AC: 4 AN: 111749 Hom.: 0 Cov.: 24 AF XY: 0.0000294 AC XY: 1 AN XY: 33965

African (AFR) AF: 0.00 AC: 0 AN: 30682

American (AMR) AF: 0.00 AC: 0 AN: 10581

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3536

South Asian (SAS) AF: 0.00 AC: 0 AN: 2624

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000752 AC: 4 AN: 53159

Other (OTH) AF: 0.00 AC: 0 AN: 1514

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.0
DANN	Benign	0.48
PhyloP100		2.2
PromoterAI		0.033	Neutral
Mutation Taster		=100/0	polymorphism

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: rs146920180; hg19: chrX-99922320;