10-69088188-C-G

Variant names:

• chr10-69088188-C-G
• rs11548212
• NM_002727.4:c.31C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002727.4(SRGN):​c.31C>G​(p.Leu11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. L11F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRGN NM_002727.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78
• Publications: 0 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]

ENSG00000297306 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRGN	NM_002727.4	MANE Select	c.31C>G	p.Leu11Val	missense	Exon 1 of 3	NP_002718.2
	SRGN	NM_001321053.2		c.31C>G	p.Leu11Val	missense	Exon 2 of 4	NP_001307982.1	P10124
	SRGN	NM_001321054.1		c.11C>G	p.Ala4Gly	missense	Exon 1 of 2	NP_001307983.1	P10124

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRGN	ENST00000242465.4	TSL:1 MANE Select	c.31C>G	p.Leu11Val	missense	Exon 1 of 3	ENSP00000242465.3	P10124
	SRGN	ENST00000718456.1		c.31C>G	p.Leu11Val	missense	Exon 1 of 3	ENSP00000520834.1	P10124
	SRGN	ENST00000462445.1	TSL:2	n.83C>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251448 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Benign	0.016
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.8
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.20
Sift	Uncertain	0.023	D
Sift4G	Benign	0.095	T
Polyphen		0.89	P
Vest4		0.33
MutPred		0.68		Loss of helix (P = 0.028)
MVP		0.76
MPC		0.59
ClinPred		0.59	D
GERP RS		2.1
PromoterAI		-0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.090
gMVP		0.18
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs11548212; hg19: chr10-70847944;