2-85694638-A-T

Variant names:

• chr2-85694638-A-T
• rs1866138
• NM_006433.5:c.52+168A>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.52+168A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GNLY NM_006433.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.513
• Publications: 7 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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNLY	NM_006433.5	c.52+168A>T		intron_variant	Intron 1 of 4	ENST00000263863.9	NP_006424.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNLY	ENST00000263863.9	c.52+168A>T		intron_variant	Intron 1 of 4	1	NM_006433.5	ENSP00000263863.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 916256 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 460244

African (AFR) AF: 0.00 AC: 0 AN: 21080

American (AMR) AF: 0.00 AC: 0 AN: 21658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16840

East Asian (EAS) AF: 0.00 AC: 0 AN: 33756

South Asian (SAS) AF: 0.00 AC: 0 AN: 57374

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2918

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 685814

Other (OTH) AF: 0.00 AC: 0 AN: 41588

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.2
DANN	Benign	0.78
PhyloP100		0.51
PromoterAI		0.016	Neutral

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: rs1866138; hg19: chr2-85921761;