NM_006488.3:c.*27A>G

Variant names:

• chr2-27099777-A-G
• rs189674797
• NM_006488.3:c.*27A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_006488.3(KHK):​c.*27A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000462 in 1,610,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: KHK NM_006488.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0970
• Publications: 0 publications found

Genes affected

KHK (HGNC:6315): (ketohexokinase) This gene encodes ketohexokinase that catalyzes conversion of fructose to fructose-1-phosphate. The product of this gene is the first enzyme with a specialized pathway that catabolizes dietary fructose. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

CGREF1 (HGNC:16962): (cell growth regulator with EF-hand domain 1) Predicted to enable calcium ion binding activity. Predicted to be involved in negative regulation of cell population proliferation. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-27099777-A-G is Benign according to our data. Variant chr2-27099777-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 335501.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006488.3. 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
	KHK	NM_006488.3	MANE Select	c.*27A>G		3_prime_UTR	Exon 8 of 8	NP_006479.1	P50053-1
	KHK	NM_000221.3		c.*27A>G		3_prime_UTR	Exon 8 of 8	NP_000212.1	P50053-2
	CGREF1	NM_001166240.2		c.*7T>C		3_prime_UTR	Exon 6 of 6	NP_001159712.1	Q99674-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KHK	ENST00000260598.10	TSL:2 MANE Select	c.*27A>G		3_prime_UTR	Exon 8 of 8	ENSP00000260598.5	P50053-1
	KHK	ENST00000260599.11	TSL:1	c.*27A>G		3_prime_UTR	Exon 8 of 8	ENSP00000260599.6	P50053-2
	KHK	ENST00000464371.1	TSL:1	n.850A>G		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes AF: 0.00251 AC: 382 AN: 152060 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00896

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000621 AC: 150 AN: 241668 AF XY: 0.000374

Gnomad AFR exome AF: 0.00825

Gnomad AMR exome AF: 0.000472

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000555

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000372

Gnomad OTH exome AF: 0.000168

GnomAD4 exome AF: 0.000248 AC: 362 AN: 1458656 Hom.: 0 Cov.: 33 AF XY: 0.000179 AC XY: 130 AN XY: 725376

African (AFR) AF: 0.00841 AC: 281 AN: 33408

American (AMR) AF: 0.000564 AC: 25 AN: 44324

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26028

East Asian (EAS) AF: 0.0000758 AC: 3 AN: 39556

South Asian (SAS) AF: 0.0000350 AC: 3 AN: 85634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53168

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5706

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1110618

Other (OTH) AF: 0.000581 AC: 35 AN: 60214

GnomAD4 genome AF: 0.00251 AC: 382 AN: 152178 Hom.: 0 Cov.: 32 AF XY: 0.00215 AC XY: 160 AN XY: 74400

African (AFR) AF: 0.00893 AC: 371 AN: 41542

American (AMR) AF: 0.000457 AC: 7 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5168

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67984

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00147 Hom.: 1

Bravo AF: 0.00282

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Essential fructosuria (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.35
PhyloP100		-0.097
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	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: rs189674797; hg19: chr2-27322645;