Genetic Variant IDNK:p.Thr89Lys (chr9-83643482-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001001551.4(IDNK):c.266C>A(p.Thr89Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T89M) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

IDNK
NM_001001551.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.260

Publications

0 publications found

Variant links:

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]

IDNK links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.053412974).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IDNK	NM_001001551.4	MANE Select	c.266C>A	p.Thr89Lys	missense	Exon 5 of 5	NP_001001551.2	Q5T6J7-1
IDNK	NM_001256915.2		c.128C>A	p.Thr43Lys	missense	Exon 5 of 5	NP_001243844.1	Q5T6J7-3
IDNK	NM_001351535.2		c.128C>A	p.Thr43Lys	missense	Exon 5 of 5	NP_001338464.1	Q5T6J7-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IDNK	ENST00000376419.5	TSL:1 MANE Select	c.266C>A	p.Thr89Lys	missense	Exon 5 of 5	ENSP00000365601.4	Q5T6J7-1
IDNK	ENST00000533522.1	TSL:1	n.*531C>A		non_coding_transcript_exon	Exon 6 of 6	ENSP00000434673.1	E9PP88
IDNK	ENST00000533522.1	TSL:1	n.*531C>A		3_prime_UTR	Exon 6 of 6	ENSP00000434673.1	E9PP88

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251242

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461750

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

1111916

Other (OTH)

AF:

0.0000331

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.8

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.0095

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.37

M_CAP

Benign

0.0031

MetaRNN

Benign

0.053

MetaSVM

Benign

-0.99

PhyloP100

0.26

PROVEAN

Benign

0.65

REVEL

Benign

0.037

Sift

Benign

0.21

Sift4G

Benign

0.22

Vest4

0.33

MutPred

0.32

Loss of sheet (P = 0.0228)

MVP

0.014

ClinPred

0.18

GERP RS

3.2

Varity_R

0.075

Mutation Taster

=80/20

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over