NM_014467.3:c.83-100T>C

Variant names:

• chrX-100650685-T-C
• rs2073164
• NM_014467.3:c.83-100T>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.83-100T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 769,784 control chromosomes in the GnomAD database, including 652 homozygotes. There are 8,106 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (200 hom., 1663 hem., cov: 22)
  • Exomes 𝑓: 0.027 (452 hom. 6443 hem.)
• Consequence: SRPX2 NM_014467.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.306
• 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: 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=-0.83).
• BP6: Variant X-100650685-T-C is Benign according to our data. Variant chrX-100650685-T-C is described in ClinVar as Benign. ClinVar VariationId is 1239134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 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.83-100T>C		intron	N/A	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.83-100T>C		intron	N/A	ENSP00000362095.3	O60687
	SRPX2	ENST00000638458.1	TSL:5	c.83-100T>C		intron	N/A	ENSP00000492168.1	A0A1W2PR88
	SRPX2	ENST00000640889.1	TSL:5	c.83-100T>C		intron	N/A	ENSP00000492571.1	A0A1W2PRB1

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 5442 AN: 111062 Hom.: 200 Cov.: 22

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0378

Gnomad ASJ AF: 0.0148

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0588

Gnomad MID AF: 0.0208

Gnomad NFE AF: 0.00741

Gnomad OTH AF: 0.0321

GnomAD4 exome AF: 0.0271 AC: 17819 AN: 658667 Hom.: 452 AF XY: 0.0345 AC XY: 6443 AN XY: 186561

African (AFR) AF: 0.125 AC: 2247 AN: 18005

American (AMR) AF: 0.0468 AC: 1414 AN: 30188

Ashkenazi Jewish (ASJ) AF: 0.0160 AC: 258 AN: 16114

East Asian (EAS) AF: 0.121 AC: 3262 AN: 27037

South Asian (SAS) AF: 0.110 AC: 4752 AN: 43171

European-Finnish (FIN) AF: 0.0559 AC: 2086 AN: 37318

Middle Eastern (MID) AF: 0.0307 AC: 102 AN: 3320

European-Non Finnish (NFE) AF: 0.00597 AC: 2700 AN: 452039

Other (OTH) AF: 0.0317 AC: 998 AN: 31475

GnomAD4 genome AF: 0.0491 AC: 5455 AN: 111117 Hom.: 200 Cov.: 22 AF XY: 0.0499 AC XY: 1663 AN XY: 33339

African (AFR) AF: 0.115 AC: 3515 AN: 30509

American (AMR) AF: 0.0375 AC: 393 AN: 10477

Ashkenazi Jewish (ASJ) AF: 0.0148 AC: 39 AN: 2639

East Asian (EAS) AF: 0.118 AC: 415 AN: 3530

South Asian (SAS) AF: 0.114 AC: 294 AN: 2568

European-Finnish (FIN) AF: 0.0588 AC: 349 AN: 5935

Middle Eastern (MID) AF: 0.0183 AC: 4 AN: 218

European-Non Finnish (NFE) AF: 0.00741 AC: 393 AN: 53043

Other (OTH) AF: 0.0350 AC: 53 AN: 1516

Alfa AF: 0.0258 Hom.: 2212

Bravo AF: 0.0526

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	-0.83
CADD	Benign	1.3
DANN	Benign	0.83
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2073164; hg19: chrX-99905682;