rs906219

Variant names:

• chr10-69266754-C-A
• rs906219
• NM_025130.4:c.2751C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-69266754-C-A
• chr10-69266754-C-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.2751C>A​(p.Asn917Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,609,906 control chromosomes in the GnomAD database, including 93,669 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.30 (7786 hom., cov: 32)
  • Exomes 𝑓: 0.34 (85883 hom.)
• Consequence: HKDC1 NM_025130.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 35 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.6474724E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.553 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.2751C>A	p.Asn917Lys	missense	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.2751C>A	p.Asn917Lys	missense	Exon 18 of 18	ENSP00000346643.5
	ENSG00000231748	ENST00000413220.1	TSL:3	n.49-1027G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45640 AN: 151934 Hom.: 7784 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.338

GnomAD2 exomes AF: 0.353 AC: 87383 AN: 247438 AF XY: 0.347

Gnomad AFR exome AF: 0.143

Gnomad AMR exome AF: 0.500

Gnomad ASJ exome AF: 0.379

Gnomad EAS exome AF: 0.536

Gnomad FIN exome AF: 0.321

Gnomad NFE exome AF: 0.339

Gnomad OTH exome AF: 0.367

GnomAD4 exome AF: 0.336 AC: 490135 AN: 1457854 Hom.: 85883 Cov.: 33 AF XY: 0.334 AC XY: 241932 AN XY: 725106

African (AFR) AF: 0.143 AC: 4770 AN: 33292

American (AMR) AF: 0.491 AC: 21497 AN: 43768

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 9955 AN: 25960

East Asian (EAS) AF: 0.586 AC: 23204 AN: 39628

South Asian (SAS) AF: 0.255 AC: 21763 AN: 85296

European-Finnish (FIN) AF: 0.318 AC: 16967 AN: 53354

Middle Eastern (MID) AF: 0.385 AC: 2216 AN: 5750

European-Non Finnish (NFE) AF: 0.332 AC: 368310 AN: 1110564

Other (OTH) AF: 0.356 AC: 21453 AN: 60242

GnomAD4 genome AF: 0.300 AC: 45655 AN: 152052 Hom.: 7786 Cov.: 32 AF XY: 0.303 AC XY: 22529 AN XY: 74310

African (AFR) AF: 0.150 AC: 6235 AN: 41496

American (AMR) AF: 0.429 AC: 6553 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1313 AN: 3472

East Asian (EAS) AF: 0.570 AC: 2933 AN: 5146

South Asian (SAS) AF: 0.261 AC: 1257 AN: 4814

European-Finnish (FIN) AF: 0.324 AC: 3425 AN: 10568

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.335 AC: 22800 AN: 67970

Other (OTH) AF: 0.337 AC: 711 AN: 2112

Alfa AF: 0.334 Hom.: 42980

Bravo AF: 0.306

TwinsUK AF: 0.347 AC: 1285

ALSPAC AF: 0.327 AC: 1262

ESP6500AA AF: 0.156 AC: 687

ESP6500EA AF: 0.353 AC: 3039

ExAC AF: 0.341 AC: 41370

Asia WGS AF: 0.422 AC: 1466 AN: 3478

EpiCase AF: 0.356

EpiControl AF: 0.361

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.00016	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.20	N
PhyloP100		1.2
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.24
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.041	D
Polyphen		0.0	B
Vest4		0.059
MutPred		0.14		Gain of MoRF binding (P = 0.0366)
MPC		0.16
ClinPred		0.0067	T
GERP RS		0.70
Varity_R		0.11
gMVP		0.43
Mutation Taster		=98/2	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: rs906219; hg19: chr10-71026510; COSMIC: COSV63580256; COSMIC: COSV63580256;