19-51371821-C-G

Variant names:

• chr19-51371821-C-G
• rs1411919017
• NM_005601.4:c.454G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005601.4(NKG7):​c.454G>C​(p.Gly152Arg) 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 1,460,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G152C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NKG7 NM_005601.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.828
• Publications: 0 publications found

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]

ENSG00000297420 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.119460374).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005601.4. 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
	NKG7	NM_005601.4	MANE Select	c.454G>C	p.Gly152Arg	missense	Exon 4 of 4	NP_005592.1	Q16617
	NKG7	NM_001363693.2		c.*6G>C		3_prime_UTR	Exon 3 of 3	NP_001350622.1	A0A0B4J2A6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKG7	ENST00000221978.10	TSL:1 MANE Select	c.454G>C	p.Gly152Arg	missense	Exon 4 of 4	ENSP00000221978.4	Q16617
	NKG7	ENST00000595157.1	TSL:1	c.223G>C	p.Gly75Arg	missense	Exon 4 of 4	ENSP00000471163.1	M0R0D6
	NKG7	ENST00000600427.5	TSL:3	c.214G>C	p.Gly72Arg	missense	Exon 3 of 3	ENSP00000469370.1	M0QXT6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250606 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460806 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726550

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86134

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111332

Other (OTH) AF: 0.00 AC: 0 AN: 60332

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.22
DANN	Benign	0.68
DEOGEN2	Benign	0.083	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.83
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.087
Sift	Benign	0.18	T
Sift4G	Benign	0.13	T
Polyphen		0.59	P
Vest4		0.11
MutPred		0.55		Gain of methylation at G152 (P = 0.0135)
MVP		0.13
MPC		0.12
ClinPred		0.54	D
GERP RS		-1.2
Varity_R		0.11
gMVP		0.59
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1411919017; hg19: chr19-51875075;