10-69097207-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002727.4(SRGN):c.203C>G(p.Pro68Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,613,808 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0097 ( 13 hom., cov: 31)

Exomes 𝑓: 0.011 ( 143 hom. )

Consequence

SRGN
NM_002727.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.523

Variant links:

Genes affected

SRGN (HGNC:9361): (serglycin) This gene encodes a protein best known as a hematopoietic cell granule proteoglycan. Proteoglycans stored in the secretory granules of many hematopoietic cells also contain a protease-resistant peptide core, which may be important for neutralizing hydrolytic enzymes. This encoded protein was found to be associated with the macromolecular complex of granzymes and perforin, which may serve as a mediator of granule-mediated apoptosis. Two transcript variants, only one of them protein-coding, have been found for this gene. [provided by RefSeq, Jul 2010]

SRGN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004487455).

BP6

Variant 10-69097207-C-G is Benign according to our data. Variant chr10-69097207-C-G is described in ClinVar as [Benign]. Clinvar id is 710351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0097 (1477/152234) while in subpopulation NFE AF= 0.0165 (1120/68016). AF 95% confidence interval is 0.0157. There are 13 homozygotes in gnomad4. There are 711 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRGN	NM_002727.4 link	c.203C>G	p.Pro68Arg	missense_variant	Exon 2 of 3	ENST00000242465.4	NP_002718.2	P10124
SRGN	NM_001321053.2 link	c.203C>G	p.Pro68Arg	missense_variant	Exon 3 of 4		NP_001307982.1	P10124
SRGN	NM_001321054.1 link	c.60-6664C>G		intron_variant	Intron 1 of 1		NP_001307983.1	P10124

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRGN	ENST00000242465.4 link	c.203C>G	p.Pro68Arg	missense_variant	Exon 2 of 3	1	NM_002727.4	ENSP00000242465.3		P10124
SRGN	ENST00000462445.1 link	n.132-6664C>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.00972

AC:

1478

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0172

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0165

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00939

AC:

2361

AN:

251346

Hom.:

AF XY:

0.00953

AC XY:

1295

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00336

Gnomad ASJ exome

AF:

0.000595

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00366

Gnomad FIN exome

AF:

0.0175

Gnomad NFE exome

AF:

0.0146

Gnomad OTH exome

AF:

0.00929

GnomAD4 exome

AF:

0.0106

AC:

15550

AN:

1461574

Hom.:

143

Cov.:

AF XY:

0.0106

AC XY:

7734

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.00119

Gnomad4 AMR exome

AF:

0.00326

Gnomad4 ASJ exome

AF:

0.000651

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00336

Gnomad4 FIN exome

AF:

0.0187

Gnomad4 NFE exome

AF:

0.0122

Gnomad4 OTH exome

AF:

0.00825

GnomAD4 genome

AF:

0.00970

AC:

1477

AN:

152234

Hom.:

Cov.:

AF XY:

0.00955

AC XY:

711

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00173

Gnomad4 AMR

AF:

0.00504

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.0172

Gnomad4 NFE

AF:

0.0165

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.0137

Hom.:

Bravo

AF:

0.00750

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.0124

AC:

107

ExAC

AF:

0.00966

AC:

1173

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0131

EpiControl

AF:

0.0122

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 26, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.60

CADD

Benign

8.8

DANN

Benign

0.89

DEOGEN2

Benign

0.37

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.58

MetaRNN

Benign

0.0045

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.90

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.063

Sift

Benign

0.12

Sift4G

Uncertain

0.056

Polyphen

0.14

Vest4

0.15

MVP

0.32

MPC

0.62

ClinPred

0.021

GERP RS

0.24

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.058

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over