Variant 7-134532005-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PP3_ModerateBS2

The NM_020299.5(AKR1B10):c.332A>G(p.His111Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000716 in 1,613,956 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00074 ( 3 hom. )

Consequence

AKR1B10
NM_020299.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.91

Variant links:

Genes affected

AKR1B10 (HGNC:382): (aldo-keto reductase family 1 member B10) This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. This member can efficiently reduce aliphatic and aromatic aldehydes, and it is less active on hexoses. It is highly expressed in adrenal gland, small intestine, and colon, and may play an important role in liver carcinogenesis. [provided by RefSeq, Jul 2008]

AKR1B10 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity AK1BA_HUMAN

PP3

MetaRNN computational evidence supports a deleterious effect, 0.841

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AKR1B10	NM_020299.5 linkuse as main transcript	c.332A>G	p.His111Arg	missense_variant	3/10	ENST00000359579.5	NP_064695.3
AKR1B10	XM_047420634.1 linkuse as main transcript	c.332A>G	p.His111Arg	missense_variant	3/9		XP_047276590.1
AKR1B10	XM_011516417.3 linkuse as main transcript	c.332A>G	p.His111Arg	missense_variant	3/5		XP_011514719.1
AKR1B10	XM_011516416.2 linkuse as main transcript	c.235-999A>G		intron_variant			XP_011514718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKR1B10	ENST00000359579.5 linkuse as main transcript	c.332A>G	p.His111Arg	missense_variant	3/10	1	NM_020299.5	ENSP00000352584	P1
AKR1B10	ENST00000475559.1 linkuse as main transcript	n.624A>G		non_coding_transcript_exon_variant	3/7	5

Frequencies

GnomAD3 genomes

AF:

0.000467

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000390

AC:

AN:

251312

Hom.:

AF XY:

0.000324

AC XY:

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000731

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000742

AC:

1085

AN:

1461802

Hom.:

Cov.:

AF XY:

0.000708

AC XY:

515

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.000927

Gnomad4 OTH exome

AF:

0.000546

GnomAD4 genome

AF:

0.000467

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.000471

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000631

Hom.:

Bravo

AF:

0.000468

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000354

AC:

EpiCase

AF:

0.000765

EpiControl

AF:

0.00101

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 18, 2023

The c.332A>G (p.H111R) alteration is located in exon 3 (coding exon 3) of the AKR1B10 gene. This alteration results from a A to G substitution at nucleotide position 332, causing the histidine (H) at amino acid position 111 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Uncertain

0.026

BayesDel_noAF

Pathogenic

0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.79

M_CAP

Benign

0.019

MetaRNN

Pathogenic

0.84

MetaSVM

Uncertain

0.23

MutationAssessor

Pathogenic

4.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-7.6

REVEL

Pathogenic

0.68

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.76

MVP

0.72

MPC

0.37

ClinPred

0.77

GERP RS

4.4

Varity_R

0.98

gMVP

0.94

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over