10-69248900-A-G

Variant names:

• chr10-69248900-A-G
• rs2279927
• NM_025130.4:c.1570+172A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025130.4(HKDC1):​c.1570+172A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 628,408 control chromosomes in the GnomAD database, including 19,825 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 0.20 (3972 hom., cov: 33)
  • Exomes 𝑓: 0.25 (15853 hom.)
• Consequence: HKDC1 NM_025130.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.663
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.272 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.1570+172A>G		intron	N/A	NP_079406.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HKDC1	ENST00000354624.6	TSL:1 MANE Select	c.1570+172A>G		intron	N/A	ENSP00000346643.5
	HKDC1	ENST00000488706.1	TSL:3	n.561A>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30448 AN: 152132 Hom.: 3969 Cov.: 33

Gnomad AFR AF: 0.0526

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.0963

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.251 AC: 119317 AN: 476158 Hom.: 15853 Cov.: 6 AF XY: 0.251 AC XY: 61614 AN XY: 245878

African (AFR) AF: 0.0493 AC: 643 AN: 13034

American (AMR) AF: 0.203 AC: 3018 AN: 14836

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 1960 AN: 13498

East Asian (EAS) AF: 0.133 AC: 4000 AN: 30154

South Asian (SAS) AF: 0.233 AC: 8838 AN: 37890

European-Finnish (FIN) AF: 0.327 AC: 9467 AN: 28954

Middle Eastern (MID) AF: 0.134 AC: 266 AN: 1984

European-Non Finnish (NFE) AF: 0.276 AC: 85311 AN: 309354

Other (OTH) AF: 0.220 AC: 5814 AN: 26454

GnomAD4 genome AF: 0.200 AC: 30447 AN: 152250 Hom.: 3972 Cov.: 33 AF XY: 0.203 AC XY: 15104 AN XY: 74440

African (AFR) AF: 0.0524 AC: 2180 AN: 41566

American (AMR) AF: 0.207 AC: 3163 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 501 AN: 3470

East Asian (EAS) AF: 0.0958 AC: 497 AN: 5190

South Asian (SAS) AF: 0.219 AC: 1056 AN: 4822

European-Finnish (FIN) AF: 0.350 AC: 3706 AN: 10584

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18735 AN: 68002

Other (OTH) AF: 0.185 AC: 391 AN: 2110

Alfa AF: 0.243 Hom.: 8048

Bravo AF: 0.181

Asia WGS AF: 0.139 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.40
DANN	Benign	0.70
PhyloP100		-0.66
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: rs2279927; hg19: chr10-71008656;