19-51372424-C-T

Variant names:

• chr19-51372424-C-T
• NM_005601.4:c.112G>A

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.112G>A​(p.Ala38Thr) 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. 15/22 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: -2.05
• 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]

LOC124904752 (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=0.11688334).

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.112G>A	p.Ala38Thr	missense	Exon 1 of 4	NP_005592.1	Q16617
	NKG7	NM_001363693.2		c.112G>A	p.Ala38Thr	missense	Exon 1 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.112G>A	p.Ala38Thr	missense	Exon 1 of 4	ENSP00000221978.4	Q16617
	NKG7	ENST00000595217.1	TSL:2	c.112G>A	p.Ala38Thr	missense	Exon 1 of 3	ENSP00000468910.1	A0A0B4J2A6
	NKG7	ENST00000600427.5	TSL:3	c.112G>A	p.Ala38Thr	missense	Exon 1 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	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	5.6
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L
PhyloP100		-2.1
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.10
Sift	Benign	0.045	D
Sift4G	Uncertain	0.037	D
Polyphen		0.63	P
Vest4		0.12
MutPred		0.53		Gain of glycosylation at A38 (P = 0.0423)
MVP		0.095
MPC		0.49
ClinPred		0.29	T
GERP RS		0.35
PromoterAI		-0.022	Neutral
Varity_R		0.056
gMVP		0.17
Mutation Taster		=95/5	polymorphism

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

hg19: chr19-51875678;