10-69103949-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_002727.4(SRGN):c.306C>T(p.Ser102=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,614,182 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (9 hom.)
• Consequence: SRGN NM_002727.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.20

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

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 10-69103949-C-T is Benign according to our data. Variant chr10-69103949-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 735160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.2 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRGN	NM_002727.4	c.306C>T	p.Ser102=	synonymous_variant	3/3	ENST00000242465.4
SRGN	NM_001321053.2	c.306C>T	p.Ser102=	synonymous_variant	4/4
SRGN	NM_001321054.1	c.138C>T	p.Ser46=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRGN	ENST00000242465.4	c.306C>T	p.Ser102=	synonymous_variant	3/3	1	NM_002727.4	P1
SRGN	ENST00000462445.1	n.210C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.00145 AC: 221 AN: 152176 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000821

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00807

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000955

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00215 AC: 540 AN: 251472 Hom.: 2 AF XY: 0.00278 AC XY: 378 AN XY: 135914

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00142

Gnomad ASJ exome AF: 0.00546

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00901

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00116

Gnomad OTH exome AF: 0.00342

GnomAD4 exome AF: 0.00137 AC: 1998 AN: 1461888 Hom.: 9 Cov.: 30 AF XY: 0.00165 AC XY: 1199 AN XY: 727248

Gnomad4 AFR exome AF: 0.000866

Gnomad4 AMR exome AF: 0.00161

Gnomad4 ASJ exome AF: 0.00547

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00914

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000682

Gnomad4 OTH exome AF: 0.00233

GnomAD4 genome AF: 0.00146 AC: 222 AN: 152294 Hom.: 1 Cov.: 32 AF XY: 0.00160 AC XY: 119 AN XY: 74454

Gnomad4 AFR AF: 0.000818

Gnomad4 AMR AF: 0.00288

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000955

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00139 Hom.: 0

Bravo AF: 0.00143

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00142

EpiControl AF: 0.00273

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2022	SRGN: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Mar 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	8.1
Dann	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs138154045; hg19: chr10-70863705;