Variant 10-69097096-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002727.4(SRGN):c.92G>A(p.Arg31Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 1,613,294 control chromosomes in the GnomAD database, including 522,340 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.70 ( 39741 hom., cov: 31)

Exomes 𝑓: 0.81 ( 482599 hom. )

Consequence

SRGN
NM_002727.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.169

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:

SRGN (HGNC:):

SRGN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.688414E-7).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRGN	NM_002727.4 linkuse as main transcript	c.92G>A	p.Arg31Gln	missense_variant	2/3	ENST00000242465.4	NP_002718.2	P10124
SRGN	NM_001321053.2 linkuse as main transcript	c.92G>A	p.Arg31Gln	missense_variant	3/4		NP_001307982.1	P10124
SRGN	NM_001321054.1 linkuse as main transcript	c.60-6775G>A		intron_variant			NP_001307983.1	P10124

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRGN	ENST00000242465.4 linkuse as main transcript	c.92G>A	p.Arg31Gln	missense_variant	2/3	1	NM_002727.4	ENSP00000242465.3		P10124
SRGN	ENST00000462445.1 linkuse as main transcript	n.132-6775G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.698

AC:

106026

AN:

151900

Hom.:

39745

Cov.:

show subpopulations

Gnomad AFR

AF:

0.413

Gnomad AMI

AF:

0.911

Gnomad AMR

AF:

0.692

Gnomad ASJ

AF:

0.887

Gnomad EAS

AF:

0.535

Gnomad SAS

AF:

0.750

Gnomad FIN

AF:

0.856

Gnomad MID

AF:

0.848

Gnomad NFE

AF:

0.841

Gnomad OTH

AF:

0.751

GnomAD3 exomes

AF:

0.755

AC:

189376

AN:

250976

Hom.:

74139

AF XY:

0.769

AC XY:

104266

AN XY:

135662

show subpopulations

Gnomad AFR exome

AF:

0.400

Gnomad AMR exome

AF:

0.621

Gnomad ASJ exome

AF:

0.900

Gnomad EAS exome

AF:

0.546

Gnomad SAS exome

AF:

0.762

Gnomad FIN exome

AF:

0.873

Gnomad NFE exome

AF:

0.839

Gnomad OTH exome

AF:

0.807

GnomAD4 exome

AF:

0.807

AC:

1179069

AN:

1461276

Hom.:

482599

Cov.:

AF XY:

0.809

AC XY:

587820

AN XY:

726970

show subpopulations

Gnomad4 AFR exome

AF:

0.391

Gnomad4 AMR exome

AF:

0.632

Gnomad4 ASJ exome

AF:

0.894

Gnomad4 EAS exome

AF:

0.512

Gnomad4 SAS exome

AF:

0.768

Gnomad4 FIN exome

AF:

0.872

Gnomad4 NFE exome

AF:

0.835

Gnomad4 OTH exome

AF:

0.791

GnomAD4 genome

AF:

0.698

AC:

106043

AN:

152018

Hom.:

39741

Cov.:

AF XY:

0.699

AC XY:

51944

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.413

Gnomad4 AMR

AF:

0.693

Gnomad4 ASJ

AF:

0.887

Gnomad4 EAS

AF:

0.535

Gnomad4 SAS

AF:

0.750

Gnomad4 FIN

AF:

0.856

Gnomad4 NFE

AF:

0.841

Gnomad4 OTH

AF:

0.745

Alfa

AF:

0.810

Hom.:

92369

Bravo

AF:

0.671

TwinsUK

AF:

0.832

AC:

3085

ALSPAC

AF:

0.837

AC:

3225

ESP6500AA

AF:

0.421

AC:

1855

ESP6500EA

AF:

0.844

AC:

7255

ExAC

AF:

0.751

AC:

91155

Asia WGS

AF:

0.609

AC:

2118

AN:

3478

EpiCase

AF:

0.845

EpiControl

AF:

0.844

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

3.4

DANN

Benign

0.79

DEOGEN2

Benign

0.071

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.38

MetaRNN

Benign

8.7e-7

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.51

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.94

REVEL

Benign

0.028

Sift

Benign

0.66

Sift4G

Benign

0.81

Polyphen

0.12

Vest4

0.035

MPC

0.23

ClinPred

0.0071

GERP RS

-0.99

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.027

gMVP

0.090

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over