Genetic Variant SRPX:p.Val419Val (chrX-38149849-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_001170752.2(SRPX):c.1135G>T(p.Gly379*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000339 in 1,208,755 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.000018 ( 0 hom. 5 hem. )

Consequence

SRPX
NM_001170752.2 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.262

Publications

0 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.

BP6

Variant X-38149849-C-A is Benign according to our data. Variant chrX-38149849-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 729004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170752.2. 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.1257G>T	p.Val419Val	synonymous	Exon 10 of 10	NP_006298.1	P78539-1
SRPX	NM_001170752.2		c.1135G>T	p.Gly379*	stop_gained	Exon 9 of 9	NP_001164223.1	P78539-4
SRPX	NM_001170750.2		c.1197G>T	p.Val399Val	synonymous	Exon 9 of 9	NP_001164221.1	P78539-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRPX	ENST00000378533.4	TSL:1 MANE Select	c.1257G>T	p.Val419Val	synonymous	Exon 10 of 10	ENSP00000367794.3	P78539-1
ENSG00000250349	ENST00000465127.1	TSL:5	c.172-516272C>A		intron	N/A	ENSP00000417050.1	B4E171
SRPX	ENST00000538295.5	TSL:2	c.1135G>T	p.Gly379*	stop_gained	Exon 9 of 9	ENSP00000445034.1	P78539-4

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

111787

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000685

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000948

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000555

AC:

AN:

180138

AF XY:

0.0000771

show subpopulations

Gnomad AFR exome

AF:

0.000691

Gnomad AMR exome

AF:

0.0000371

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000182

AC:

AN:

1096915

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

362325

show subpopulations

African (AFR)

AF:

0.000607

AC:

AN:

26372

American (AMR)

AF:

0.0000285

AC:

AN:

35068

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19355

East Asian (EAS)

AF:

0.00

AC:

AN:

30147

South Asian (SAS)

AF:

0.00

AC:

AN:

53745

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40477

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4127

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841573

Other (OTH)

AF:

0.0000651

AC:

AN:

46051

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

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:

0.000188

AC:

AN:

111840

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

AN XY:

34022

show subpopulations

African (AFR)

AF:

0.000683

AC:

AN:

30743

American (AMR)

AF:

0.00

AC:

AN:

10566

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2648

East Asian (EAS)

AF:

0.00

AC:

AN:

3564

South Asian (SAS)

AF:

0.00

AC:

AN:

2622

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6069

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53200

Other (OTH)

AF:

0.00

AC:

AN:

1529

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.0000411

Hom.:

Bravo

AF:

0.000246

ESP6500AA

AF:

0.00104

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

6.8

(source)

DANN

Uncertain

0.98

FATHMM_MKL

Uncertain

0.84

PhyloP100

0.26

Vest4

0.37

GERP RS

2.1

Mutation Taster

=125/75

polymorphism

(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

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