Genetic Variant IDNK:p.Pro4Leu (chr9-83623182-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001256915.2(IDNK):c.-302C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,413,506 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: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000040 ( 0 hom. )

Consequence

IDNK
NM_001256915.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.277

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.13600296).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256915.2. 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.11C>T	p.Pro4Leu	missense	Exon 1 of 5	NP_001001551.2	Q5T6J7-1
IDNK	NM_001256915.2		c.-302C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_001243844.1	Q5T6J7-3
IDNK	NM_001351535.2		c.-200C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 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.11C>T	p.Pro4Leu	missense	Exon 1 of 5	ENSP00000365601.4	Q5T6J7-1
IDNK	ENST00000533522.1	TSL:1	n.11C>T		non_coding_transcript_exon	Exon 1 of 6	ENSP00000434673.1	E9PP88
IDNK	ENST00000454393.5	TSL:3	c.-302C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000403290.2	Q5T6J7-3

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

151908

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000396

AC:

AN:

1261484

Hom.:

Cov.:

AF XY:

0.00000162

AC XY:

AN XY:

616406

show subpopulations

African (AFR)

AF:

0.000124

AC:

AN:

24270

American (AMR)

AF:

0.00

AC:

AN:

12296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18308

East Asian (EAS)

AF:

0.00

AC:

AN:

27716

South Asian (SAS)

AF:

0.00

AC:

AN:

57406

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43732

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4576

European-Non Finnish (NFE)

AF:

0.00000196

AC:

AN:

1021488

Other (OTH)

AF:

0.00

AC:

AN:

51692

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.415

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

AF:

0.0000658

AC:

AN:

152022

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41502

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5132

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67906

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000529

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.032

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.53

M_CAP

Benign

0.040

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

0.28

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-10

REVEL

Benign

0.067

Sift

Uncertain

0.0020

Sift4G

Benign

0.10

Polyphen

0.67

Vest4

0.24

MutPred

0.35

Loss of disorder (P = 0.0289)

MVP

0.27

MPC

0.18

ClinPred

0.98

GERP RS

2.6

PromoterAI

0.048

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.067

gMVP

0.64

Mutation Taster

=95/5

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over