NM_006433.5:c.52+168A>G

Variant names:

• chr2-85694638-A-G
• rs1866138
• NM_006433.5:c.52+168A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006433.5(GNLY):​c.52+168A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 1,066,024 control chromosomes in the GnomAD database, including 111,874 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 0.50 (19628 hom., cov: 34)
  • Exomes 𝑓: 0.45 (92246 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

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.52+168A>G		intron	N/A	NP_006424.2
	GNLY	NM_001302758.2		c.52+168A>G		intron	N/A	NP_001289687.1
	GNLY	NM_012483.4		c.-237-115A>G		intron	N/A	NP_036615.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNLY	ENST00000263863.9	TSL:1 MANE Select	c.52+168A>G		intron	N/A	ENSP00000263863.5
	GNLY	ENST00000409696.7	TSL:1	c.-237-115A>G		intron	N/A	ENSP00000387116.3
	GNLY	ENST00000464298.5	TSL:1	n.144-115A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75923 AN: 151936 Hom.: 19610 Cov.: 34

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.507

GnomAD4 exome AF: 0.446 AC: 407201 AN: 913970 Hom.: 92246 Cov.: 12 AF XY: 0.444 AC XY: 203769 AN XY: 459102

African (AFR) AF: 0.639 AC: 13438 AN: 21026

American (AMR) AF: 0.484 AC: 10468 AN: 21626

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 8992 AN: 16826

East Asian (EAS) AF: 0.574 AC: 19343 AN: 33710

South Asian (SAS) AF: 0.379 AC: 21716 AN: 57262

European-Finnish (FIN) AF: 0.409 AC: 14388 AN: 35204

Middle Eastern (MID) AF: 0.485 AC: 1413 AN: 2916

European-Non Finnish (NFE) AF: 0.436 AC: 298050 AN: 683902

Other (OTH) AF: 0.467 AC: 19393 AN: 41498

GnomAD4 genome AF: 0.500 AC: 75987 AN: 152054 Hom.: 19628 Cov.: 34 AF XY: 0.496 AC XY: 36905 AN XY: 74332

African (AFR) AF: 0.630 AC: 26145 AN: 41498

American (AMR) AF: 0.473 AC: 7237 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1811 AN: 3472

East Asian (EAS) AF: 0.584 AC: 2999 AN: 5138

South Asian (SAS) AF: 0.384 AC: 1853 AN: 4826

European-Finnish (FIN) AF: 0.412 AC: 4355 AN: 10576

Middle Eastern (MID) AF: 0.503 AC: 147 AN: 292

European-Non Finnish (NFE) AF: 0.439 AC: 29819 AN: 67936

Other (OTH) AF: 0.507 AC: 1072 AN: 2116

Alfa AF: 0.455 Hom.: 11060

Bravo AF: 0.515

Asia WGS AF: 0.496 AC: 1721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.5
DANN	Benign	0.75
PhyloP100		0.51
PromoterAI		0.017	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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;