Genetic Variant NM_005601.4:c.217G>A (chr19-51372248-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005601.4(NKG7):c.217G>A(p.Val73Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000239 in 1,613,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V73L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

NKG7
NM_005601.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.64

Publications

2 publications found

Variant links:

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]

NKG7 links:

LOC124904752 (HGNC:):

LOC124904752 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.045572758).

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.217G>A	p.Val73Met	missense	Exon 2 of 4	NP_005592.1	Q16617
	NKG7	NM_001363693.2		c.158-46G>A		intron	N/A	NP_001350622.1	A0A0B4J2A6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NKG7	ENST00000221978.10	TSL:1 MANE Select	c.217G>A	p.Val73Met	missense	Exon 2 of 4	ENSP00000221978.4	Q16617
NKG7	ENST00000595157.1	TSL:1	c.32-46G>A		intron	N/A	ENSP00000471163.1	M0R0D6
NKG7	ENST00000595217.1	TSL:2	c.158-46G>A		intron	N/A	ENSP00000468910.1	A0A0B4J2A6

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000299

AC:

AN:

250682

AF XY:

0.000303

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00251

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000380

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000237

AC:

347

AN:

1461422

Hom.:

Cov.:

AF XY:

0.000246

AC XY:

179

AN XY:

727008

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33480

American (AMR)

AF:

0.0000448

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00207

AC:

AN:

26062

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000128

AC:

AN:

86192

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000221

AC:

246

AN:

1111774

Other (OTH)

AF:

0.000381

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

100

125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000250

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41450

American (AMR)

AF:

0.0000654

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00260

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000368

AC:

AN:

68026

Other (OTH)

AF:

0.000478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000412

Hom.:

Bravo

AF:

0.000253

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000354

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000830

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.40

CADD

Benign

0.61

(source)

DANN

Benign

0.65

DEOGEN2

Uncertain

0.42

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.65

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.046

MetaSVM

Benign

-0.61

MutationAssessor

Benign

1.4

PhyloP100

-1.6

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.99

REVEL

Benign

0.17

Sift

Benign

0.20

Sift4G

Benign

0.17

Polyphen

0.15

Vest4

0.20

MVP

0.16

MPC

0.10

ClinPred

0.017

GERP RS

-3.9

PromoterAI

-0.018

Neutral

(source)

Varity_R

0.041

gMVP

0.34

Mutation Taster

=98/2

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over