NM_001001551.4:c.39C>T

Variant names:

• chr9-83623210-C-T
• rs1464963715
• NM_001001551.4:c.39C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001001551.4(IDNK):​c.39C>T​(p.Ser13Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000159 in 1,255,164 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: IDNK NM_001001551.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• Publications: 0 publications found

Genes affected

IDNK (HGNC:31367): (IDNK gluconokinase) Predicted to enable gluconokinase activity. Predicted to be involved in D-gluconate catabolic process. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001551.4. 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
	IDNK	NM_001001551.4	MANE Select	c.39C>T	p.Ser13Ser	synonymous	Exon 1 of 5	NP_001001551.2	Q5T6J7-1
	IDNK	NM_001256915.2		c.-274C>T		5_prime_UTR	Exon 1 of 5	NP_001243844.1	Q5T6J7-3
	IDNK	NM_001351535.2		c.-172C>T		5_prime_UTR	Exon 1 of 5	NP_001338464.1	Q5T6J7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDNK	ENST00000376419.5	TSL:1 MANE Select	c.39C>T	p.Ser13Ser	synonymous	Exon 1 of 5	ENSP00000365601.4	Q5T6J7-1
	IDNK	ENST00000533522.1	TSL:1	n.33+6C>T		splice_region intron	N/A	ENSP00000434673.1	E9PP88
	IDNK	ENST00000904784.1		c.39C>T	p.Ser13Ser	synonymous	Exon 1 of 5	ENSP00000574843.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000159 AC: 2 AN: 1255164 Hom.: 0 Cov.: 33 AF XY: 0.00000327 AC XY: 2 AN XY: 611794

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24132

American (AMR) AF: 0.00 AC: 0 AN: 11398

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17884

East Asian (EAS) AF: 0.00 AC: 0 AN: 27638

South Asian (SAS) AF: 0.00 AC: 0 AN: 56564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4694

European-Non Finnish (NFE) AF: 0.00000197 AC: 2 AN: 1017694

Other (OTH) AF: 0.00 AC: 0 AN: 51366

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Benign	0.94
PhyloP100		1.4
PromoterAI		0.38	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=54/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.60		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.60		Position offset: -6
DS_DL_spliceai		0.43		Position offset: 11

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

Other links and lift over

dbSNP: rs1464963715; hg19: chr9-86238125;