rs121918363

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_014467.3(SRPX2):​c.980A>C​(p.Asn327Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,098,171 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 24)
Exomes š‘“: 0.0000027 ( 0 hom. 2 hem. )

Consequence

SRPX2
NM_014467.3 missense

Scores

7
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.70
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SRPX2NM_014467.3 linkc.980A>C p.Asn327Thr missense_variant Exon 9 of 11 ENST00000373004.5 NP_055282.1 O60687

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SRPX2ENST00000373004.5 linkc.980A>C p.Asn327Thr missense_variant Exon 9 of 11 1 NM_014467.3 ENSP00000362095.3 O60687

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD4 exome
AF:
0.00000273
AC:
3
AN:
1098171
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
2
AN XY:
363529
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000356
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.067
T;.
FATHMM_MKL
Benign
0.57
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Uncertain
0.15
D
MetaRNN
Uncertain
0.47
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;.
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-1.1
N;.
REVEL
Benign
0.10
Sift
Uncertain
0.014
D;.
Sift4G
Uncertain
0.053
T;.
Polyphen
0.24
B;.
Vest4
0.41
MutPred
0.84
Gain of glycosylation at N327 (P = 0.0952);.;
MVP
0.33
MPC
0.17
ClinPred
0.67
D
GERP RS
5.5
Varity_R
0.24
gMVP
0.27

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-99922289; API