chr2-85697606-C-G

Variant names:

• chr2-85697606-C-G
• rs11127
• NM_006433.5:c.356C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006433.5(GNLY):​c.356C>G​(p.Thr119Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GNLY NM_006433.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.582
• Publications: 47 publications found

Genes affected

GNLY (HGNC:4414): (granulysin) The product of this gene is a member of the saposin-like protein (SAPLIP) family and is located in the cytotoxic granules of T cells, which are released upon antigen stimulation. This protein is present in cytotoxic granules of cytotoxic T lymphocytes and natural killer cells, and it has antimicrobial activity against M. tuberculosis and other organisms. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ENSG00000310473 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056510657).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006433.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNLY	NM_006433.5	MANE Select	c.356C>G	p.Thr119Ser	missense	Exon 4 of 5	NP_006424.2
	GNLY	NM_001302758.2		c.437C>G	p.Thr146Ser	missense	Exon 5 of 6	NP_001289687.1
	GNLY	NM_012483.4		c.311C>G	p.Thr104Ser	missense	Exon 5 of 6	NP_036615.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNLY	ENST00000263863.9	TSL:1 MANE Select	c.356C>G	p.Thr119Ser	missense	Exon 4 of 5	ENSP00000263863.5
	GNLY	ENST00000409696.7	TSL:1	c.311C>G	p.Thr104Ser	missense	Exon 5 of 6	ENSP00000387116.3
	GNLY	ENST00000526018.1	TSL:5	c.254C>G	p.Thr85Ser	missense	Exon 3 of 5	ENSP00000434467.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460836 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726806

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5672

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111148

Other (OTH) AF: 0.00 AC: 0 AN: 60354

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	0.70
DANN	Benign	0.13
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.58
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.11
Sift	Benign	0.64	T
Sift4G	Benign	0.42	T
Polyphen		0.011	B
Vest4		0.051
MutPred		0.53		Gain of disorder (P = 0.0508)
MVP		0.49
MPC		0.092
ClinPred		0.043	T
GERP RS		0.27
Varity_R		0.079
gMVP		0.46
Mutation Taster		=97/3	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: rs11127; hg19: chr2-85924729;