dbSNP rs2805910: SRGN:p.Arg31Gln (chr10-69097096-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_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. 15/21 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 0.70 ( 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

Publications

28 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002727.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRGN	NM_002727.4	MANE Select	c.92G>A	p.Arg31Gln	missense	Exon 2 of 3	NP_002718.2
SRGN	NM_001321053.2		c.92G>A	p.Arg31Gln	missense	Exon 3 of 4	NP_001307982.1	P10124
SRGN	NM_001321054.1		c.60-6775G>A		intron	N/A	NP_001307983.1	P10124

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRGN	ENST00000242465.4	TSL:1 MANE Select	c.92G>A	p.Arg31Gln	missense	Exon 2 of 3	ENSP00000242465.3	P10124
SRGN	ENST00000718456.1		c.92G>A	p.Arg31Gln	missense	Exon 2 of 3	ENSP00000520834.1	P10124
SRGN	ENST00000462445.1	TSL:2	n.132-6775G>A		intron	N/A

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

GnomAD2 exomes

AF:

0.755

AC:

189376

AN:

250976

AF XY:

0.769

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 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

African (AFR)

AF:

0.391

AC:

13082

AN:

33458

American (AMR)

AF:

0.632

AC:

28227

AN:

44654

Ashkenazi Jewish (ASJ)

AF:

0.894

AC:

23339

AN:

26116

East Asian (EAS)

AF:

0.512

AC:

20316

AN:

39670

South Asian (SAS)

AF:

0.768

AC:

66192

AN:

86176

European-Finnish (FIN)

AF:

0.872

AC:

46566

AN:

53406

Middle Eastern (MID)

AF:

0.842

AC:

4856

AN:

5766

European-Non Finnish (NFE)

AF:

0.835

AC:

928743

AN:

1111664

Other (OTH)

AF:

0.791

AC:

47748

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

10261

20521

30782

41042

51303

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20876

41752

62628

83504

104380

<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:

0.698

AC:

106043

AN:

152018

Hom.:

39741

Cov.:

AF XY:

0.699

AC XY:

51944

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.413

AC:

17080

AN:

41388

American (AMR)

AF:

0.693

AC:

10564

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.887

AC:

3079

AN:

3470

East Asian (EAS)

AF:

0.535

AC:

2769

AN:

5176

South Asian (SAS)

AF:

0.750

AC:

3610

AN:

4816

European-Finnish (FIN)

AF:

0.856

AC:

9082

AN:

10604

Middle Eastern (MID)

AF:

0.837

AC:

246

AN:

294

European-Non Finnish (NFE)

AF:

0.841

AC:

57216

AN:

68002

Other (OTH)

AF:

0.745

AC:

1568

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1346

2692

4038

5384

6730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

800

1600

2400

3200

4000

<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:

0.791

Hom.:

185908

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

3.4

(source)

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

PhyloP100

-0.17

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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