10-69300865-C-T

Variant names:

• chr10-69300865-C-T
• rs1108272
• NM_001358263.1:c.75+5185C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033500.2(HK1):​c.27+4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0767 in 1,458,266 control chromosomes in the GnomAD database, including 8,975 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1295 hom., cov: 33)
  • Exomes 𝑓: 0.074 (7680 hom.)
• Consequence: HK1 NM_033500.2 splice_region, intron
• Scores: Splicing: ADA: 0.00001420
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.07
• Publications: 5 publications found

Genes affected

HK1 (HGNC:4922): (hexokinase 1) Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. This gene encodes a ubiquitous form of hexokinase which localizes to the outer membrane of mitochondria. Mutations in this gene have been associated with hemolytic anemia due to hexokinase deficiency. Alternative splicing of this gene results in several transcript variants which encode different isoforms, some of which are tissue-specific. [provided by RefSeq, Apr 2016]

RPS15AP28 (HGNC:36381): (ribosomal protein S15a pseudogene 28)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.1).
• BP6: Variant 10-69300865-C-T is Benign according to our data. Variant chr10-69300865-C-T is described in ClinVar as Benign. ClinVar VariationId is 994066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033500.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HK1	NM_001358263.1	MANE Plus Clinical	c.75+5185C>T		intron	N/A	NP_001345192.1	P19367-3
	HK1	NM_001322365.2		c.168+5185C>T		intron	N/A	NP_001309294.1
	HK1	NM_001322364.2		c.75+5185C>T		intron	N/A	NP_001309293.1	P19367-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HK1	ENST00000643399.2	MANE Plus Clinical	c.75+5185C>T		intron	N/A	ENSP00000494664.1	P19367-3
	HK1	ENST00000464803.6	TSL:1	c.168+5185C>T		intron	N/A	ENSP00000496531.1	A0A2R8Y7T9
	HK1	ENST00000480047.5	TSL:1	n.379+5185C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15478 AN: 151924 Hom.: 1289 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.0593

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.0844

Gnomad FIN AF: 0.0938

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0539

Gnomad OTH AF: 0.104

GnomAD2 exomes AF: 0.114 AC: 26982 AN: 237364 AF XY: 0.105

Gnomad AFR exome AF: 0.125

Gnomad AMR exome AF: 0.167

Gnomad ASJ exome AF: 0.117

Gnomad EAS exome AF: 0.492

Gnomad FIN exome AF: 0.0867

Gnomad NFE exome AF: 0.0518

Gnomad OTH exome AF: 0.0937

GnomAD4 exome AF: 0.0737 AC: 96327 AN: 1306224 Hom.: 7680 Cov.: 19 AF XY: 0.0724 AC XY: 47543 AN XY: 657076

African (AFR) AF: 0.121 AC: 3682 AN: 30398

American (AMR) AF: 0.164 AC: 7050 AN: 42880

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 2876 AN: 25104

East Asian (EAS) AF: 0.485 AC: 18822 AN: 38848

South Asian (SAS) AF: 0.0674 AC: 5563 AN: 82566

European-Finnish (FIN) AF: 0.0846 AC: 4474 AN: 52886

Middle Eastern (MID) AF: 0.0534 AC: 292 AN: 5466

European-Non Finnish (NFE) AF: 0.0499 AC: 48536 AN: 972896

Other (OTH) AF: 0.0912 AC: 5032 AN: 55180

GnomAD4 genome AF: 0.102 AC: 15496 AN: 152042 Hom.: 1295 Cov.: 33 AF XY: 0.106 AC XY: 7842 AN XY: 74318

African (AFR) AF: 0.126 AC: 5233 AN: 41418

American (AMR) AF: 0.134 AC: 2048 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 384 AN: 3468

East Asian (EAS) AF: 0.476 AC: 2464 AN: 5174

South Asian (SAS) AF: 0.0849 AC: 409 AN: 4816

European-Finnish (FIN) AF: 0.0938 AC: 991 AN: 10560

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0539 AC: 3669 AN: 68018

Other (OTH) AF: 0.105 AC: 222 AN: 2110

Alfa AF: 0.0577 Hom.: 191

Bravo AF: 0.108

Asia WGS AF: 0.290 AC: 1006 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.1
DANN	Benign	0.63
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000014
dbscSNV1_RF	Benign	0.0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1108272; hg19: chr10-71060621;