X-100662151-G-T

Variant names:

• chrX-100662151-G-T
• rs41293523
• NM_014467.3:c.164-25G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014467.3(SRPX2):​c.164-25G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00341 in 1,200,038 control chromosomes in the GnomAD database, including 95 homozygotes. There are 1,074 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (48 hom., 514 hem., cov: 23)
  • Exomes 𝑓: 0.0019 (47 hom. 560 hem.)
• Consequence: SRPX2 NM_014467.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.281
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant X-100662151-G-T is Benign according to our data. Variant chrX-100662151-G-T is described in ClinVar as Benign. ClinVar VariationId is 1294336.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0589 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.164-25G>T		intron	N/A	NP_055282.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRPX2	ENST00000373004.5	TSL:1 MANE Select	c.164-25G>T		intron	N/A	ENSP00000362095.3
	SRPX2	ENST00000638458.1	TSL:5	c.164-1G>T		splice_acceptor intron	N/A	ENSP00000492168.1
	SRPX2	ENST00000640889.1	TSL:5	c.164-25G>T		intron	N/A	ENSP00000492571.1

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 1978 AN: 110846 Hom.: 48 Cov.: 23

Gnomad AFR AF: 0.0612

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00850

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: 0.000264

Gnomad OTH AF: 0.0101

GnomAD2 exomes AF: 0.00516 AC: 940 AN: 182000 AF XY: 0.00375

Gnomad AFR exome AF: 0.0638

Gnomad AMR exome AF: 0.00288

Gnomad ASJ exome AF: 0.000134

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000861

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00193 AC: 2105 AN: 1089147 Hom.: 47 Cov.: 29 AF XY: 0.00158 AC XY: 560 AN XY: 355117

African (AFR) AF: 0.0654 AC: 1715 AN: 26221

American (AMR) AF: 0.00352 AC: 124 AN: 35194

Ashkenazi Jewish (ASJ) AF: 0.000103 AC: 2 AN: 19331

East Asian (EAS) AF: 0.00 AC: 0 AN: 30168

South Asian (SAS) AF: 0.000130 AC: 7 AN: 53953

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40127

Middle Eastern (MID) AF: 0.00171 AC: 7 AN: 4096

European-Non Finnish (NFE) AF: 0.0000743 AC: 62 AN: 834247

Other (OTH) AF: 0.00410 AC: 188 AN: 45810

GnomAD4 genome AF: 0.0179 AC: 1983 AN: 110891 Hom.: 48 Cov.: 23 AF XY: 0.0155 AC XY: 514 AN XY: 33175

African (AFR) AF: 0.0612 AC: 1865 AN: 30465

American (AMR) AF: 0.00849 AC: 89 AN: 10478

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3538

South Asian (SAS) AF: 0.00 AC: 0 AN: 2611

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5819

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.000264 AC: 14 AN: 52930

Other (OTH) AF: 0.00997 AC: 15 AN: 1505

Alfa AF: 0.00582 Hom.: 43

Bravo AF: 0.0207

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0558 AC: 214

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.00574 AC: 697

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.54
FATHMM_MKL	Benign	0.17	N
PhyloP100		0.28
GERP RS		3.2
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: rs41293523; hg19: chrX-99917148;