chr10-69104641-G-T

Position:

• chr10-69104641-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002727.4(SRGN):​c.*521G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 152,320 control chromosomes in the GnomAD database, including 348 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.063 (348 hom., cov: 32)
  • Exomes 𝑓: 0.057 (0 hom.)
• Consequence: SRGN NM_002727.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRGN	NM_002727.4	c.*521G>T		3_prime_UTR_variant	3/3	ENST00000242465.4
SRGN	NM_001321053.2	c.*521G>T		3_prime_UTR_variant	4/4
SRGN	NM_001321054.1	c.*521G>T		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRGN	ENST00000242465.4	c.*521G>T		3_prime_UTR_variant	3/3	1	NM_002727.4	P1

Frequencies

GnomAD3 genomes AF: 0.0626 AC: 9524 AN: 152064 Hom.: 345 Cov.: 32

Gnomad AFR AF: 0.0560

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.0759

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0344

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0610

Gnomad OTH AF: 0.0651

GnomAD4 exome AF: 0.0571 AC: 8 AN: 140 Hom.: 0 Cov.: 0 AF XY: 0.0333 AC XY: 3 AN XY: 90

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0678

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0626 AC: 9520 AN: 152180 Hom.: 348 Cov.: 32 AF XY: 0.0634 AC XY: 4718 AN XY: 74382

Gnomad4 AFR AF: 0.0559

Gnomad4 AMR AF: 0.0759

Gnomad4 ASJ AF: 0.0282

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.0344

Gnomad4 NFE AF: 0.0610

Gnomad4 OTH AF: 0.0639

Alfa AF: 0.0577 Hom.: 48

Bravo AF: 0.0634

Asia WGS AF: 0.115 AC: 402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.2
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7377; hg19: chr10-70864397;