19-51372176-C-A

Variant names:

• chr19-51372176-C-A
• rs532047087
• NM_005601.4:c.289G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005601.4(NKG7):​c.289G>T​(p.Ala97Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. A97T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NKG7 NM_005601.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056154102).

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.289G>T	p.Ala97Ser	missense	Exon 2 of 4	NP_005592.1	Q16617
	NKG7	NM_001363693.2		c.184G>T	p.Ala62Ser	missense	Exon 2 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.289G>T	p.Ala97Ser	missense	Exon 2 of 4	ENSP00000221978.4	Q16617
	NKG7	ENST00000595157.1	TSL:1	c.58G>T	p.Ala20Ser	missense	Exon 2 of 4	ENSP00000471163.1	M0R0D6
	NKG7	ENST00000595217.1	TSL:2	c.184G>T	p.Ala62Ser	missense	Exon 2 of 3	ENSP00000468910.1	A0A0B4J2A6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455314 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723420

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33384

American (AMR) AF: 0.00 AC: 0 AN: 44166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25412

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 85004

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108736

Other (OTH) AF: 0.00 AC: 0 AN: 60108

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.2
DANN	Benign	0.89
DEOGEN2	Benign	0.22	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	-0.90	N
PhyloP100		-1.1
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.11
Sift	Benign	0.39	T
Sift4G	Benign	0.39	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.46		Gain of glycosylation at A97 (P = 0.0155)
MVP		0.22
MPC		0.13
ClinPred		0.039	T
GERP RS		-4.4
PromoterAI		0.0068	Neutral
Varity_R		0.043
gMVP		0.24
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs532047087; hg19: chr19-51875430;