chr2-85697606-C-T

Position:

• chr2-85697606-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000263863.9(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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.32 (9008 hom., cov: 33)
  • Exomes 𝑓: 0.38 (108650 hom.)
• Consequence: GNLY ENST00000263863.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.582

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNLY	NM_006433.5	c.356C>T	p.Thr119Ile	missense_variant	4/5	ENST00000263863.9	NP_006424.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNLY	ENST00000263863.9	c.356C>T	p.Thr119Ile	missense_variant	4/5	1	NM_006433.5	ENSP00000263863	P2

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

GnomAD3 exomes AF: 0.388 AC: 97431 AN: 251328 Hom.: 19995 AF XY: 0.390 AC XY: 53041 AN XY: 135832

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 SAS exome AF: 0.367

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

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.415

Gnomad4 ASJ exome AF: 0.467

Gnomad4 EAS exome AF: 0.584

Gnomad4 SAS exome AF: 0.370

Gnomad4 FIN exome AF: 0.373

Gnomad4 NFE exome AF: 0.379

Gnomad4 OTH exome AF: 0.383

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

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.585

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.378

Alfa AF: 0.385 Hom.: 29965

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 v4.3

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;T;T
MetaRNN	Benign	0.000017	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.1	L;.;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.049
Sift	Benign	0.24	T;T;T
Sift4G	Benign	0.15	T;T;T
Polyphen		0.026	B;B;.
Vest4		0.093
MPC		0.023
ClinPred		0.0043	T
GERP RS		0.27
Varity_R		0.047
gMVP		0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs11127; hg19: chr2-85924729; COSMIC: COSV55702827; COSMIC: COSV55702827;