2-85697261-C-T

Variant names:

• chr2-85697261-C-T
• rs1561285
• NM_006433.5:c.256-245C>T

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.256-245C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000059 in 338,704 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000059 (0 hom.)
• Consequence: GNLY NM_006433.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 9 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 (BayesDel_noAF=-0.89).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNLY	NM_006433.5	MANE Select	c.256-245C>T		intron	N/A	NP_006424.2
	GNLY	NM_001302758.2		c.337-245C>T		intron	N/A	NP_001289687.1	B4E3H9
	GNLY	NM_012483.4		c.211-245C>T		intron	N/A	NP_036615.2	P22749-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNLY	ENST00000263863.9	TSL:1 MANE Select	c.256-245C>T		intron	N/A	ENSP00000263863.5	P22749-1
	GNLY	ENST00000409696.7	TSL:1	c.211-245C>T		intron	N/A	ENSP00000387116.3	P22749-2
	GNLY	ENST00000526018.1	TSL:5	c.154-245C>T		intron	N/A	ENSP00000434467.1	H0YDW8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000590 AC: 2 AN: 338704 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 177068

African (AFR) AF: 0.00 AC: 0 AN: 10376

American (AMR) AF: 0.00 AC: 0 AN: 14630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10754

East Asian (EAS) AF: 0.0000441 AC: 1 AN: 22686

South Asian (SAS) AF: 0.00 AC: 0 AN: 36284

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20674

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1524

European-Non Finnish (NFE) AF: 0.00000495 AC: 1 AN: 201856

Other (OTH) AF: 0.00 AC: 0 AN: 19920

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.90
PhyloP100		0.0040

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: rs1561285; hg19: chr2-85924384;