rs2229498

Variant names:

• chr10-69097096-G-A
• rs2229498
• NM_002727.4:c.92G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169
• Publications: 28 publications found

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]

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRGN	NM_002727.4	c.92G>A	p.Arg31Gln	missense_variant	Exon 2 of 3	ENST00000242465.4	NP_002718.2
SRGN	NM_001321053.2	c.92G>A	p.Arg31Gln	missense_variant	Exon 3 of 4		NP_001307982.1
SRGN	NM_001321054.1	c.60-6775G>A		intron_variant	Intron 1 of 1		NP_001307983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRGN	ENST00000242465.4	c.92G>A	p.Arg31Gln	missense_variant	Exon 2 of 3	1	NM_002727.4	ENSP00000242465.3
SRGN	ENST00000718456.1	c.92G>A	p.Arg31Gln	missense_variant	Exon 2 of 3			ENSP00000520834.1
SRGN	ENST00000462445.1	n.132-6775G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106026 AN: 151900 Hom.: 39745 Cov.: 31

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

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.: 44 AF XY: 0.809 AC XY: 587820 AN XY: 726970

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

GnomAD4 genome AF: 0.698 AC: 106043 AN: 152018 Hom.: 39741 Cov.: 31 AF XY: 0.699 AC XY: 51944 AN XY: 74308

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

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 v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.4
DANN	Benign	0.79
DEOGEN2	Benign	0.071	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.38	T
MetaRNN	Benign	8.7e-7	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.51	N
PhyloP100		-0.17
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.028
Sift	Benign	0.66	T
Sift4G	Benign	0.81	T
Polyphen		0.12	B
Vest4		0.035
MPC		0.23
ClinPred		0.0071	T
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)

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

Other links and lift over

dbSNP: rs2229498; hg19: chr10-70856852; COSMIC: COSV54345640; COSMIC: COSV54345640;