Variant 7-134575423-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080538.3(AKR1B15):c.517A>G(p.Met173Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000706 in 1,613,794 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 1 hom. )

Consequence

AKR1B15
NM_001080538.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.26

Variant links:

Genes affected

AKR1B15 (HGNC:37281): (aldo-keto reductase family 1 member B15) Enables estradiol 17-beta-dehydrogenase activity. Predicted to be involved in estrogen biosynthetic process. Located in cytosol and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

AKR1B15 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18632525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKR1B15	NM_001080538.3 linkuse as main transcript	c.517A>G	p.Met173Val	missense_variant	7/12	ENST00000457545.7	NP_001074007.2	C9JRZ8-2
AKR1B15	NM_001367820.1 linkuse as main transcript	c.517A>G	p.Met173Val	missense_variant	6/11		NP_001354749.1
AKR1B15	NM_001367821.1 linkuse as main transcript	c.433A>G	p.Met145Val	missense_variant	6/11		NP_001354750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AKR1B15	ENST00000457545.7 linkuse as main transcript	c.517A>G	p.Met173Val	missense_variant	7/12	5	NM_001080538.3	ENSP00000389289.1	C9JRZ8-2
AKR1B15	ENST00000423958.2 linkuse as main transcript	c.517A>G	p.Met173Val	missense_variant	5/10	5		ENSP00000397009.2	C9JRZ8-2
AKR1B15	ENST00000652743.1 linkuse as main transcript	c.433A>G	p.Met145Val	missense_variant	5/10			ENSP00000498877.1	C9JRZ8-1

Frequencies

GnomAD3 genomes

AF:

0.000453

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000918

AC:

AN:

250658

Hom.:

AF XY:

0.0000738

AC XY:

AN XY:

135466

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000308

AC:

AN:

1461492

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

727058

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000453

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00156

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000103

Hom.:

Bravo

AF:

0.000457

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

AC:

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

Jul 20, 2021

The c.517A>G (p.M173V) alteration is located in exon 7 (coding exon 5) of the AKR1B15 gene. This alteration results from a A to G substitution at nucleotide position 517, causing the methionine (M) at amino acid position 173 to be replaced by a valine (V). 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

Benign

0.23

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.73

.;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.8

D;.

REVEL

Benign

0.25

Sift

Uncertain

0.010

D;.

Sift4G

Uncertain

0.0040

D;D

Vest4

0.66

MVP

0.20

MPC

0.14

ClinPred

0.17

GERP RS

2.3

gMVP

0.55

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