9-83623210-C-G

Variant names:

• chr9-83623210-C-G
• NM_001001551.4:c.39C>G
• IDNK p.Ser13Arg

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>G​(p.Ser13Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IDNK NM_001001551.4 missense
• 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: Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, BayesDel_addAF, Cadd, FATHMM_MKL, M_CAP, MutationAssessor, PrimateAI, PROVEAN [when MetaRNN, MutationTaster, phyloP100way_vertebrate was below the threshold]

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>G	p.Ser13Arg	missense	Exon 1 of 5	NP_001001551.2	Q5T6J7-1
	IDNK	NM_001256915.2		c.-274C>G		5_prime_UTR	Exon 1 of 5	NP_001243844.1	Q5T6J7-3
	IDNK	NM_001351535.2		c.-172C>G		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>G	p.Ser13Arg	missense	Exon 1 of 5	ENSP00000365601.4	Q5T6J7-1
	IDNK	ENST00000533522.1	TSL:1	n.33+6C>G		splice_region intron	N/A	ENSP00000434673.1	E9PP88
	IDNK	ENST00000904784.1		c.39C>G	p.Ser13Arg	missense	Exon 1 of 5	ENSP00000574843.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1255166 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 611794

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: 43796

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1017694

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	34
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.42	T
M_CAP	Pathogenic	0.44	D
MetaRNN	Benign	0.40	T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Pathogenic	4.2	H
PhyloP100		1.4
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
PromoterAI		-0.24	Neutral
Varity_R		0.82
gMVP		0.88
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: -15
DS_DL_spliceai		0.23		Position offset: 11

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-86238125;