rs796052175

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PM2PP3_StrongBP6

The NM_025130.4(HKDC1):​c.1001T>A​(p.Ile334Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HKDC1
NM_025130.4 missense

Scores

8
10
1

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.92
Variant links:
Genes affected
HKDC1 (HGNC:23302): (hexokinase domain containing 1) This gene encodes a member of the hexokinase protein family. The encoded protein is involved in glucose metabolism, and reduced expression may be associated with gestational diabetes mellitus. High expression of this gene may also be associated with poor prognosis in hepatocarcinoma. [provided by RefSeq, Sep 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.962
BP6
Variant 10-69246204-T-A is Benign according to our data. Variant chr10-69246204-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 207898.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HKDC1NM_025130.4 linkuse as main transcriptc.1001T>A p.Ile334Asn missense_variant 8/18 ENST00000354624.6 NP_079406.4 Q2TB90-1B3KT70
HKDC1XM_011540195.3 linkuse as main transcriptc.1001T>A p.Ile334Asn missense_variant 8/16 XP_011538497.1
HKDC1XM_047425784.1 linkuse as main transcriptc.425T>A p.Ile142Asn missense_variant 5/15 XP_047281740.1
HKDC1XR_007061989.1 linkuse as main transcriptn.1105T>A non_coding_transcript_exon_variant 8/18

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HKDC1ENST00000354624.6 linkuse as main transcriptc.1001T>A p.Ile334Asn missense_variant 8/181 NM_025130.4 ENSP00000346643.5 Q2TB90-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461782
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727182
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Long QT syndrome Benign:1
Likely benign, no assertion criteria providedresearchMedical Research Institute, Tokyo Medical and Dental University-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.39
D
BayesDel_noAF
Pathogenic
0.32
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.63
D
Eigen
Uncertain
0.68
Eigen_PC
Uncertain
0.60
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.96
D
M_CAP
Uncertain
0.22
D
MetaRNN
Pathogenic
0.96
D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Uncertain
2.9
M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.61
T
PROVEAN
Uncertain
-3.7
D
REVEL
Pathogenic
0.94
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0070
D
Polyphen
1.0
D
Vest4
0.90
MutPred
0.80
Gain of disorder (P = 0.0205);
MVP
0.97
MPC
0.80
ClinPred
1.0
D
GERP RS
4.7
Varity_R
0.78
gMVP
0.89

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: rs796052175; hg19: chr10-71005960; API