chr6-125957062-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138571.5(HINT3):​c.85G>C​(p.Val29Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,398,480 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. V29M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

HINT3
NM_138571.5 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.10

Publications

0 publications found
Variant links:
Genes affected
HINT3 (HGNC:18468): (histidine triad nucleotide binding protein 3) Histidine triad proteins, such as HINT3, are nucleotide hydrolases and transferases that act on the alpha-phosphate of ribonucleotides (Brenner, 2002 [PubMed 12119013]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.043952674).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HINT3NM_138571.5 linkc.85G>C p.Val29Leu missense_variant Exon 1 of 5 ENST00000229633.7 NP_612638.3 Q9NQE9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HINT3ENST00000229633.7 linkc.85G>C p.Val29Leu missense_variant Exon 1 of 5 1 NM_138571.5 ENSP00000229633.5 Q9NQE9

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD2 exomes
AF:
0.00000649
AC:
1
AN:
154164
AF XY:
0.0000122
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000170
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000286
AC:
4
AN:
1398480
Hom.:
0
Cov.:
29
AF XY:
0.00000290
AC XY:
2
AN XY:
689788
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31588
American (AMR)
AF:
0.00
AC:
0
AN:
35700
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25168
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35732
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79236
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
48554
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5698
European-Non Finnish (NFE)
AF:
0.00000371
AC:
4
AN:
1078826
Other (OTH)
AF:
0.00
AC:
0
AN:
57978
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
34
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.095
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
0.013
DANN
Benign
0.33
DEOGEN2
Benign
0.0031
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.0048
N
LIST_S2
Benign
0.37
T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.044
T
MetaSVM
Benign
-0.66
T
MutationAssessor
Benign
0.20
N
PhyloP100
-1.1
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.080
N
REVEL
Benign
0.13
Sift
Benign
0.87
T
Sift4G
Benign
0.47
T
Polyphen
0.017
B
Vest4
0.036
MutPred
0.21
Loss of loop (P = 0.0203);
MVP
0.68
MPC
0.056
ClinPred
0.059
T
GERP RS
-7.2
PromoterAI
0.0072
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.074
gMVP
0.19
Mutation Taster
=100/0
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

Publications

Other links and lift over

dbSNP: rs147213100; hg19: chr6-126278208; API