chrX-100654343-G-T

Variant names:

• chrX-100654343-G-T
• rs6616171
• NM_014467.3:c.163+3478G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014467.3(SRPX2):​c.163+3478G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.60 (15919 hom., 18968 hem., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: SRPX2 NM_014467.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590
• Publications: 1 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRPX2	NM_014467.3	c.163+3478G>T		intron_variant	Intron 3 of 10	ENST00000373004.5	NP_055282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRPX2	ENST00000373004.5	c.163+3478G>T		intron_variant	Intron 3 of 10	1	NM_014467.3	ENSP00000362095.3

Frequencies

GnomAD3 genomes AF: 0.603 AC: 66030 AN: 109492 Hom.: 15932 Cov.: 21

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.795

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.641

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.603 AC: 66026 AN: 109544 Hom.: 15919 Cov.: 21 AF XY: 0.595 AC XY: 18968 AN XY: 31868

African (AFR) AF: 0.280 AC: 8463 AN: 30210

American (AMR) AF: 0.722 AC: 7374 AN: 10215

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 1990 AN: 2615

East Asian (EAS) AF: 0.635 AC: 2173 AN: 3422

South Asian (SAS) AF: 0.538 AC: 1357 AN: 2521

European-Finnish (FIN) AF: 0.672 AC: 3820 AN: 5683

Middle Eastern (MID) AF: 0.798 AC: 170 AN: 213

European-Non Finnish (NFE) AF: 0.747 AC: 39235 AN: 52497

Other (OTH) AF: 0.639 AC: 956 AN: 1497

Alfa AF: 0.458 Hom.: 2373

Bravo AF: 0.596

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.6
DANN	Benign	0.76
PhyloP100		0.059
Mutation Taster		=100/0	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: rs6616171; hg19: chrX-99909340;