NM_005601.4:c.454G>T

Variant names:

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

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>T​(p.Gly152Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NKG7 NM_005601.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.084311694).

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>T	p.Gly152Cys	missense	Exon 4 of 4	NP_005592.1	Q16617
	NKG7	NM_001363693.2		c.*6G>T		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>T	p.Gly152Cys	missense	Exon 4 of 4	ENSP00000221978.4	Q16617
	NKG7	ENST00000595157.1	TSL:1	c.223G>T	p.Gly75Cys	missense	Exon 4 of 4	ENSP00000471163.1	M0R0D6
	NKG7	ENST00000600427.5	TSL:3	c.214G>T	p.Gly72Cys	missense	Exon 3 of 3	ENSP00000469370.1	M0QXT6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.47
DANN	Benign	0.95
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.83
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.023
Sift	Uncertain	0.015	D
Sift4G	Benign	0.064	T
Polyphen		0.014	B
Vest4		0.18
MutPred		0.49		Loss of disorder (P = 0.0297)
MVP		0.17
MPC		0.20
ClinPred		0.11	T
GERP RS		-1.2
Varity_R		0.11
gMVP		0.43
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;