dbSNP rs374467231: SRPX:p.Gln364Lys (chrX-38154583-G-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_006307.5(SRPX):c.1090C>A(p.Gln364Lys) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,205,933 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 36 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.000099 ( 0 hom. 34 hem. )

Consequence

SRPX
NM_006307.5 missense, splice_region

Scores

Splicing: ADA: 0.8577

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.56

Publications

2 publications found

Variant links:

Genes affected

SRPX (HGNC:11309): (sushi repeat containing protein X-linked) Predicted to be an extracellular matrix structural constituent. Predicted to be involved in cell adhesion. Predicted to act upstream of or within several processes, including negative regulation of cell proliferation involved in contact inhibition; phagolysosome assembly; and positive regulation of extrinsic apoptotic signaling pathway in absence of ligand. Part of collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

SRPX links:

ENSG00000250349 (HGNC:):

ENSG00000250349 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34780177).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006307.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRPX	NM_006307.5	MANE Select	c.1090C>A	p.Gln364Lys	missense splice_region	Exon 9 of 10	NP_006298.1	P78539-1
SRPX	NM_001170750.2		c.1030C>A	p.Gln344Lys	missense splice_region	Exon 8 of 9	NP_001164221.1	P78539-5
SRPX	NM_001170751.2		c.913C>A	p.Gln305Lys	missense splice_region	Exon 8 of 9	NP_001164222.1	P78539-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRPX	ENST00000378533.4	TSL:1 MANE Select	c.1090C>A	p.Gln364Lys	missense splice_region	Exon 9 of 10	ENSP00000367794.3	P78539-1
ENSG00000250349	ENST00000465127.1	TSL:5	c.172-511538G>T		intron	N/A	ENSP00000417050.1	B4E171
SRPX	ENST00000898757.1		c.1162C>A	p.Gln388Lys	missense splice_region	Exon 10 of 11	ENSP00000568816.1

Frequencies

GnomAD3 genomes

AF:

0.000116

AC:

AN:

111660

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000473

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:

0.000113

Gnomad OTH

AF:

0.000664

GnomAD2 exomes

AF:

0.0000693

AC:

AN:

173271

AF XY:

0.0000683

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000114

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000104

Gnomad OTH exome

AF:

0.000231

GnomAD4 exome

AF:

0.0000987

AC:

108

AN:

1094273

Hom.:

Cov.:

AF XY:

0.0000945

AC XY:

AN XY:

359967

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26305

American (AMR)

AF:

0.000115

AC:

AN:

34639

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19271

East Asian (EAS)

AF:

0.00

AC:

AN:

30094

South Asian (SAS)

AF:

0.00

AC:

AN:

52946

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40322

Middle Eastern (MID)

AF:

0.000731

AC:

AN:

4103

European-Non Finnish (NFE)

AF:

0.000112

AC:

AN:

840642

Other (OTH)

AF:

0.000152

AC:

AN:

45951

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000116

AC:

AN:

111660

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

33814

show subpopulations

African (AFR)

AF:

0.0000326

AC:

AN:

30665

American (AMR)

AF:

0.000473

AC:

AN:

10561

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2640

East Asian (EAS)

AF:

0.00

AC:

AN:

3554

South Asian (SAS)

AF:

0.00

AC:

AN:

2633

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6025

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.000113

AC:

AN:

53157

Other (OTH)

AF:

0.000664

AC:

AN:

1506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.000189

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000742

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.048

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

M_CAP

Pathogenic

0.60

MetaRNN

Benign

0.35

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.84

PhyloP100

9.6

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.49

REVEL

Benign

0.17

Sift

Benign

0.19

Sift4G

Benign

0.48

Polyphen

0.63

Vest4

0.42

MVP

0.79

MPC

0.075

ClinPred

0.087

GERP RS

5.6

Varity_R

0.61

gMVP

0.41

Mutation Taster

=37/63

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.86

dbscSNV1_RF

Benign

0.68

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over