rs874556

Variant names:

• chr10-69232908-C-A
• rs874556
• NM_025130.4:c.371C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-69232908-C-A
• chr10-69232908-C-G
• chr10-69232908-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025130.4(HKDC1):​c.371C>A​(p.Thr124Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HKDC1 NM_025130.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• Publications: 0 publications found

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]

HKDC1 Gene-Disease associations (from GenCC):

• retinitis pigmentosa

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11868253).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HKDC1	NM_025130.4	c.371C>A	p.Thr124Lys	missense_variant	Exon 3 of 18	ENST00000354624.6	NP_079406.4
HKDC1	XM_011540195.3	c.371C>A	p.Thr124Lys	missense_variant	Exon 3 of 16		XP_011538497.1
HKDC1	XR_007061989.1	n.475C>A		non_coding_transcript_exon_variant	Exon 3 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HKDC1	ENST00000354624.6	c.371C>A	p.Thr124Lys	missense_variant	Exon 3 of 18	1	NM_025130.4	ENSP00000346643.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 60

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	17
DANN	Benign	0.85
DEOGEN2	Benign	0.39	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.067	T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.12	T
MetaSVM	Uncertain	0.48	D
MutationAssessor	Benign	0.48	N
PhyloP100		2.0
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.34
Sift	Benign	0.52	T
Sift4G	Benign	0.62	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.57		Loss of catalytic residue at T124 (P = 0.027);
MVP		0.61
MPC		0.17
ClinPred		0.053	T
GERP RS		1.7
Varity_R		0.20
gMVP		0.54
Mutation Taster		=93/7	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

Other links and lift over

dbSNP: rs874556; hg19: chr10-70992664;