17-8369412-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001304947.3(KRBA2):​c.955G>A​(p.Val319Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,614,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

KRBA2
NM_001304947.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.122
Variant links:
Genes affected
KRBA2 (HGNC:26989): (KRAB-A domain containing 2) Predicted to enable nucleic acid binding activity. Predicted to be involved in DNA integration and regulation of transcription, DNA-templated. [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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03785637).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRBA2NM_001304947.3 linkc.955G>A p.Val319Ile missense_variant Exon 2 of 2 ENST00000396267.3 NP_001291876.1 Q6ZNG9A8MX02
KRBA2NM_213597.3 linkc.1201G>A p.Val401Ile missense_variant Exon 2 of 2 NP_998762.1 Q6ZNG9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRBA2ENST00000396267.3 linkc.955G>A p.Val319Ile missense_variant Exon 2 of 2 2 NM_001304947.3 ENSP00000379565.3 A8MX02
ENSG00000263809ENST00000582471.1 linkn.*1938G>A non_coding_transcript_exon_variant Exon 6 of 6 5 ENSP00000463847.1 J3QQQ9
ENSG00000263809ENST00000582471.1 linkn.*1938G>A 3_prime_UTR_variant Exon 6 of 6 5 ENSP00000463847.1 J3QQQ9

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152222
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000796
AC:
20
AN:
251380
Hom.:
0
AF XY:
0.0000810
AC XY:
11
AN XY:
135862
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000376
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000301
AC:
44
AN:
1461884
Hom.:
0
Cov.:
31
AF XY:
0.0000358
AC XY:
26
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152222
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000741
AC:
9

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 04, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1201G>A (p.V401I) alteration is located in exon 2 (coding exon 2) of the KRBA2 gene. This alteration results from a G to A substitution at nucleotide position 1201, causing the valine (V) at amino acid position 401 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.074
BayesDel_addAF
Benign
-0.53
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
8.8
DANN
Benign
0.93
DEOGEN2
Benign
0.011
.;T;T;T;.
Eigen
Benign
-0.85
Eigen_PC
Benign
-0.94
FATHMM_MKL
Benign
0.027
N
LIST_S2
Benign
0.45
.;T;T;.;T
M_CAP
Benign
0.0014
T
MetaRNN
Benign
0.038
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
.;.;M;M;.
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.37
.;N;N;.;.
REVEL
Benign
0.041
Sift
Benign
0.25
.;T;T;.;.
Sift4G
Benign
0.30
.;T;T;.;.
Polyphen
0.20
.;.;B;B;.
Vest4
0.024, 0.058
MutPred
0.37
.;.;Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);.;
MVP
0.11
MPC
0.13
ClinPred
0.017
T
GERP RS
-0.40
Varity_R
0.016
gMVP
0.083

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs774276819; hg19: chr17-8272730; API