dbSNP rs35318931: SRPX:p.Ser413Phe (chrX-38149868-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006307.5(SRPX):c.1238C>T(p.Ser413Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0707 in 1,203,841 control chromosomes in the GnomAD database, including 2,529 homozygotes. There are 26,479 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.049 ( 153 hom., 1485 hem., cov: 23)

Exomes 𝑓: 0.073 ( 2376 hom. 24994 hem. )

Consequence

SRPX
NM_006307.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.36

Publications

22 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008332968).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRPX	NM_006307.5 link	c.1238C>T	p.Ser413Phe	missense_variant	Exon 10 of 10	ENST00000378533.4	NP_006298.1	P78539-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRPX	ENST00000378533.4 link	c.1238C>T	p.Ser413Phe	missense_variant	Exon 10 of 10	1	NM_006307.5	ENSP00000367794.3		P78539-1
ENSG00000250349	ENST00000465127.1 link	c.172-516253G>A		intron_variant	Intron 3 of 8	5		ENSP00000417050.1		B4E171

Frequencies

GnomAD3 genomes

AF:

0.0492

AC:

5491

AN:

111652

Hom.:

153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0114

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0318

Gnomad ASJ

AF:

0.0413

Gnomad EAS

AF:

0.000281

Gnomad SAS

AF:

0.0107

Gnomad FIN

AF:

0.0572

Gnomad MID

AF:

0.0169

Gnomad NFE

AF:

0.0796

Gnomad OTH

AF:

0.0406

GnomAD2 exomes

AF:

0.0491

AC:

8460

AN:

172224

AF XY:

0.0483

show subpopulations

Gnomad AFR exome

AF:

0.0103

Gnomad AMR exome

AF:

0.0220

Gnomad ASJ exome

AF:

0.0571

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0559

Gnomad NFE exome

AF:

0.0773

Gnomad OTH exome

AF:

0.0540

GnomAD4 exome

AF:

0.0729

AC:

79646

AN:

1092138

Hom.:

2376

Cov.:

AF XY:

0.0698

AC XY:

24994

AN XY:

357868

show subpopulations

African (AFR)

AF:

0.00801

AC:

210

AN:

26209

American (AMR)

AF:

0.0236

AC:

807

AN:

34196

Ashkenazi Jewish (ASJ)

AF:

0.0524

AC:

1003

AN:

19149

East Asian (EAS)

AF:

0.0000333

AC:

AN:

30036

South Asian (SAS)

AF:

0.0189

AC:

988

AN:

52334

European-Finnish (FIN)

AF:

0.0604

AC:

2438

AN:

40376

Middle Eastern (MID)

AF:

0.00613

AC:

AN:

4076

European-Non Finnish (NFE)

AF:

0.0851

AC:

71488

AN:

839903

Other (OTH)

AF:

0.0586

AC:

2686

AN:

45859

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

2633

5266

7898

10531

13164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2704

5408

8112

10816

13520

<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:

0.0492

AC:

5493

AN:

111703

Hom.:

153

Cov.:

AF XY:

0.0438

AC XY:

1485

AN XY:

33895

show subpopulations

African (AFR)

AF:

0.0114

AC:

351

AN:

30767

American (AMR)

AF:

0.0318

AC:

336

AN:

10572

Ashkenazi Jewish (ASJ)

AF:

0.0413

AC:

109

AN:

2642

East Asian (EAS)

AF:

0.000281

AC:

AN:

3553

South Asian (SAS)

AF:

0.0115

AC:

AN:

2613

European-Finnish (FIN)

AF:

0.0572

AC:

346

AN:

6046

Middle Eastern (MID)

AF:

0.0185

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.0796

AC:

4229

AN:

53097

Other (OTH)

AF:

0.0401

AC:

AN:

1520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

202

404

606

808

1010

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0692

Hom.:

4553

Bravo

AF:

0.0455

TwinsUK

AF:

0.0917

AC:

340

ALSPAC

AF:

0.0886

AC:

256

ESP6500AA

AF:

0.0117

AC:

ESP6500EA

AF:

0.0789

AC:

531

ExAC

AF:

0.0480

AC:

5825

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.72

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.084

.;.;T

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.87

D;D;D

MetaRNN

Benign

0.0083

T;T;T

MetaSVM

Benign

-1.0

PhyloP100

3.4

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.41

N;N;N

REVEL

Benign

0.095

Sift

Benign

0.30

T;T;T

Sift4G

Benign

0.67

T;T;T

Polyphen

0.94

.;.;P

Vest4

0.29

MPC

0.12

ClinPred

0.021

GERP RS

5.2

Varity_R

0.31

gMVP

0.44

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over