10-69267475-G-C

Variant names:

• chr10-69267475-G-C
• rs2611
• NM_025130.4:c.*718G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_025130.4(HKDC1):​c.*718G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 454,846 control chromosomes in the GnomAD database, including 35,653 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.39 (11594 hom., cov: 32)
  • Exomes 𝑓: 0.39 (24059 hom.)
• Consequence: HKDC1 NM_025130.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115
• Publications: 12 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

ENSG00000231748 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.021).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025130.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HKDC1	NM_025130.4	MANE Select	c.*718G>C		3_prime_UTR	Exon 18 of 18	NP_079406.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HKDC1	ENST00000354624.6	TSL:1 MANE Select	c.*718G>C		3_prime_UTR	Exon 18 of 18	ENSP00000346643.5
	ENSG00000231748	ENST00000413220.1	TSL:3	n.48+626C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58548 AN: 151914 Hom.: 11577 Cov.: 32

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.390

GnomAD2 exomes AF: 0.379 AC: 52529 AN: 138766 AF XY: 0.392

Gnomad AFR exome AF: 0.451

Gnomad AMR exome AF: 0.274

Gnomad ASJ exome AF: 0.447

Gnomad EAS exome AF: 0.371

Gnomad FIN exome AF: 0.316

Gnomad NFE exome AF: 0.360

Gnomad OTH exome AF: 0.375

GnomAD4 exome AF: 0.389 AC: 117792 AN: 302814 Hom.: 24059 Cov.: 0 AF XY: 0.403 AC XY: 69517 AN XY: 172482

African (AFR) AF: 0.450 AC: 3846 AN: 8538

American (AMR) AF: 0.274 AC: 7432 AN: 27108

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 4714 AN: 10756

East Asian (EAS) AF: 0.350 AC: 3208 AN: 9160

South Asian (SAS) AF: 0.514 AC: 30520 AN: 59394

European-Finnish (FIN) AF: 0.320 AC: 4103 AN: 12834

Middle Eastern (MID) AF: 0.442 AC: 1014 AN: 2296

European-Non Finnish (NFE) AF: 0.363 AC: 57550 AN: 158582

Other (OTH) AF: 0.382 AC: 5405 AN: 14146

GnomAD4 genome AF: 0.386 AC: 58611 AN: 152032 Hom.: 11594 Cov.: 32 AF XY: 0.384 AC XY: 28570 AN XY: 74334

African (AFR) AF: 0.456 AC: 18890 AN: 41432

American (AMR) AF: 0.315 AC: 4811 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1528 AN: 3472

East Asian (EAS) AF: 0.338 AC: 1754 AN: 5182

South Asian (SAS) AF: 0.521 AC: 2508 AN: 4812

European-Finnish (FIN) AF: 0.309 AC: 3261 AN: 10568

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24508 AN: 67982

Other (OTH) AF: 0.393 AC: 828 AN: 2106

Alfa AF: 0.388 Hom.: 2458

Bravo AF: 0.384

Asia WGS AF: 0.408 AC: 1418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.1
DANN	Benign	0.78
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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: rs2611; hg19: chr10-71027231; COSMIC: COSV63577520; COSMIC: COSV63577520;