2-85697606-C-T

Variant names:

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

Variant summary

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

The NM_006433.5(GNLY):​c.356C>T​(p.Thr119Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,611,704 control chromosomes in the GnomAD database, including 117,658 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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: 𝑓 0.32 (9008 hom., cov: 33)
  • Exomes 𝑓: 0.38 (108650 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.7444972E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNLY	NM_006433.5	MANE Select	c.356C>T	p.Thr119Ile	missense	Exon 4 of 5	NP_006424.2
	GNLY	NM_001302758.2		c.437C>T	p.Thr146Ile	missense	Exon 5 of 6	NP_001289687.1	B4E3H9
	GNLY	NM_012483.4		c.311C>T	p.Thr104Ile	missense	Exon 5 of 6	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.356C>T	p.Thr119Ile	missense	Exon 4 of 5	ENSP00000263863.5	P22749-1
	GNLY	ENST00000409696.7	TSL:1	c.311C>T	p.Thr104Ile	missense	Exon 5 of 6	ENSP00000387116.3	P22749-2
	GNLY	ENST00000526018.1	TSL:5	c.254C>T	p.Thr85Ile	missense	Exon 3 of 5	ENSP00000434467.1	H0YDW8

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48405 AN: 152042 Hom.: 9006 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.379

GnomAD2 exomes AF: 0.388 AC: 97431 AN: 251328 AF XY: 0.390

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.412

Gnomad ASJ exome AF: 0.461

Gnomad EAS exome AF: 0.581

Gnomad FIN exome AF: 0.376

Gnomad NFE exome AF: 0.391

Gnomad OTH exome AF: 0.397

GnomAD4 exome AF: 0.381 AC: 555477 AN: 1459544 Hom.: 108650 Cov.: 32 AF XY: 0.382 AC XY: 277260 AN XY: 726216

African (AFR) AF: 0.100 AC: 3346 AN: 33466

American (AMR) AF: 0.415 AC: 18546 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 12200 AN: 26120

East Asian (EAS) AF: 0.584 AC: 23168 AN: 39686

South Asian (SAS) AF: 0.370 AC: 31900 AN: 86220

European-Finnish (FIN) AF: 0.373 AC: 19901 AN: 53412

Middle Eastern (MID) AF: 0.406 AC: 2300 AN: 5666

European-Non Finnish (NFE) AF: 0.379 AC: 421016 AN: 1109950

Other (OTH) AF: 0.383 AC: 23100 AN: 60318

GnomAD4 genome AF: 0.318 AC: 48402 AN: 152160 Hom.: 9008 Cov.: 33 AF XY: 0.321 AC XY: 23858 AN XY: 74390

African (AFR) AF: 0.111 AC: 4630 AN: 41544

American (AMR) AF: 0.391 AC: 5982 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1570 AN: 3470

East Asian (EAS) AF: 0.585 AC: 3020 AN: 5160

South Asian (SAS) AF: 0.380 AC: 1837 AN: 4832

European-Finnish (FIN) AF: 0.375 AC: 3968 AN: 10574

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26136 AN: 67978

Other (OTH) AF: 0.378 AC: 799 AN: 2112

Alfa AF: 0.375 Hom.: 51499

Bravo AF: 0.314

TwinsUK AF: 0.361 AC: 1337

ALSPAC AF: 0.369 AC: 1421

ESP6500AA AF: 0.111 AC: 491

ESP6500EA AF: 0.382 AC: 3285

ExAC AF: 0.382 AC: 46402

Asia WGS AF: 0.454 AC: 1574 AN: 3478

EpiCase AF: 0.398

EpiControl AF: 0.396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	5.4
DANN	Benign	0.81
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.40	T
MetaRNN	Benign	0.000017	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.58
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.049
Sift	Benign	0.24	T
Sift4G	Benign	0.15	T
Polyphen		0.026	B
Vest4		0.093
MPC		0.023
ClinPred		0.0043	T
GERP RS		0.27
Varity_R		0.047
gMVP		0.35
Mutation Taster		=98/2	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: rs11127; hg19: chr2-85924729; COSMIC: COSV55702827; COSMIC: COSV55702827;