19-51372176-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_005601.4(NKG7):​c.289G>A​(p.Ala97Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,607,564 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

NKG7
NM_005601.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.06
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.020512104).
BP6
Variant 19-51372176-C-T is Benign according to our data. Variant chr19-51372176-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2471501.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NKG7NM_005601.4 linkc.289G>A p.Ala97Thr missense_variant Exon 2 of 4 ENST00000221978.10 NP_005592.1 Q16617

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NKG7ENST00000221978.10 linkc.289G>A p.Ala97Thr missense_variant Exon 2 of 4 1 NM_005601.4 ENSP00000221978.4 Q16617

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152132
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000327
AC:
8
AN:
244676
Hom.:
0
AF XY:
0.0000379
AC XY:
5
AN XY:
131906
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000294
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000137
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000271
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000213
AC:
31
AN:
1455314
Hom.:
0
Cov.:
31
AF XY:
0.0000194
AC XY:
14
AN XY:
723420
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000706
Gnomad4 FIN exome
AF:
0.0000377
Gnomad4 NFE exome
AF:
0.0000207
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152250
Hom.:
0
Cov.:
32
AF XY:
0.0000537
AC XY:
4
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000473
Bravo
AF:
0.0000151
ExAC
AF:
0.0000412
AC:
5

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Feb 23, 2023
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.074
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
3.9
DANN
Benign
0.92
DEOGEN2
Benign
0.19
.;T;.
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.0079
N
LIST_S2
Benign
0.35
T;T;T
M_CAP
Benign
0.036
D
MetaRNN
Benign
0.021
T;T;T
MetaSVM
Benign
-0.81
T
MutationAssessor
Benign
-1.4
.;N;.
PrimateAI
Benign
0.26
T
PROVEAN
Benign
1.2
.;N;.
REVEL
Benign
0.14
Sift
Benign
1.0
.;T;.
Sift4G
Benign
0.49
T;T;T
Polyphen
0.0
.;B;.
Vest4
0.12
MVP
0.34
MPC
0.093
ClinPred
0.031
T
GERP RS
-4.4
Varity_R
0.023
gMVP
0.20

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs532047087; hg19: chr19-51875430; COSMIC: COSV52467330; COSMIC: COSV52467330; API