19-51371824-G-T

Position:

• chr19-51371824-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005601.4(NKG7):​c.451C>A​(p.Leu151Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NKG7 NM_005601.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.81

Genes affected

NKG7 (HGNC:7830): (natural killer cell granule protein 7) Predicted to be integral component of plasma membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21809298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NKG7	NM_005601.4	c.451C>A	p.Leu151Met	missense_variant	4/4	ENST00000221978.10
NKG7	XM_005258955.4	c.346C>A	p.Leu116Met	missense_variant	4/4
NKG7	XM_006723228.4	c.304C>A	p.Leu102Met	missense_variant	3/3
NKG7	NM_001363693.2	c.*3C>A		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NKG7	ENST00000221978.10	c.451C>A	p.Leu151Met	missense_variant	4/4	1	NM_005601.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460684 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726474

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2023

The c.451C>A (p.L151M) alteration is located in exon 4 (coding exon 4) of the NKG7 gene. This alteration results from a C to A substitution at nucleotide position 451, causing the leucine (L) at amino acid position 151 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T;.;.
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.56	T;T;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.4	M;.;.
MutationTaster	Benign	0.77	N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.94	N;.;.
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D;.;.
Sift4G	Pathogenic	0.0	D;D;T
Polyphen		1.0	D;.;.
Vest4		0.23
MutPred		0.32		Loss of glycosylation at S150 (P = 0.0555);.;.;
MVP		0.10
MPC		0.48
ClinPred		0.95	D
GERP RS		4.1
Varity_R		0.21
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-51875078;