Genetic Variant NM_006307.5:c.731G>C (chrX-38160977-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3PP5BS2

The NM_006307.5(SRPX):c.731G>C(p.Arg244Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000439 in 1,206,910 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000047 ( 0 hom. 17 hem. )

Consequence

SRPX
NM_006307.5 missense

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.06

Publications

1 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 -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.818

PP5

Variant X-38160977-C-G is Pathogenic according to our data. Variant chrX-38160977-C-G is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 599603.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAdExome4 at 17 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.731G>C	p.Arg244Thr	missense	Exon 6 of 10	NP_006298.1	P78539-1
SRPX	NM_001170750.2		c.671G>C	p.Arg224Thr	missense	Exon 5 of 9	NP_001164221.1	P78539-5
SRPX	NM_001170751.2		c.554G>C	p.Arg185Thr	missense	Exon 5 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.731G>C	p.Arg244Thr	missense	Exon 6 of 10	ENSP00000367794.3	P78539-1
ENSG00000250349	ENST00000465127.1	TSL:5	c.172-505144C>G		intron	N/A	ENSP00000417050.1	B4E171
SRPX	ENST00000898757.1		c.731G>C	p.Arg244Thr	missense	Exon 6 of 11	ENSP00000568816.1

Frequencies

GnomAD3 genomes

AF:

0.00000897

AC:

AN:

111434

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000109

AC:

AN:

183030

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000475

AC:

AN:

1095476

Hom.:

Cov.:

AF XY:

0.0000471

AC XY:

AN XY:

361028

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26380

American (AMR)

AF:

0.00

AC:

AN:

35178

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19317

East Asian (EAS)

AF:

0.00

AC:

AN:

30187

South Asian (SAS)

AF:

0.00

AC:

AN:

53367

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40434

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4037

European-Non Finnish (NFE)

AF:

0.0000595

AC:

AN:

840594

Other (OTH)

AF:

0.0000435

AC:

AN:

45982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

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:

0.00000897

AC:

AN:

111434

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33624

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30570

American (AMR)

AF:

0.00

AC:

AN:

10465

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.00

AC:

AN:

3570

South Asian (SAS)

AF:

0.00

AC:

AN:

2591

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6043

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53126

Other (OTH)

AF:

0.00

AC:

AN:

1500

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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:

0.00

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Likely pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Short stature (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Benign

-0.014

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.098

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

M_CAP

Pathogenic

0.62

MetaRNN

Pathogenic

0.82

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

7.1

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-2.3

REVEL

Benign

0.20

Sift

Benign

0.067

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.83

MutPred

0.67

Loss of MoRF binding (P = 0.0278)

MVP

0.91

MPC

0.17

ClinPred

0.67

GERP RS

5.9

Varity_R

0.80

gMVP

0.77

Mutation Taster

=43/57

disease causing (ClinVar)

(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