Variant 7-134575915-C-T 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.731C>T(p.Pro244Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00012 in 1,613,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

AKR1B15
NM_001080538.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.71

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=0.13276932).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AKR1B15	NM_001080538.3 linkuse as main transcript	c.731C>T	p.Pro244Leu	missense_variant	8/12	ENST00000457545.7
AKR1B15	NM_001367820.1 linkuse as main transcript	c.731C>T	p.Pro244Leu	missense_variant	7/11
AKR1B15	NM_001367821.1 linkuse as main transcript	c.647C>T	p.Pro216Leu	missense_variant	7/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1B15	ENST00000457545.7 linkuse as main transcript	c.731C>T	p.Pro244Leu	missense_variant	8/12	5	NM_001080538.3		C9JRZ8-2
AKR1B15	ENST00000423958.2 linkuse as main transcript	c.731C>T	p.Pro244Leu	missense_variant	6/10	5			C9JRZ8-2
AKR1B15	ENST00000652743.1 linkuse as main transcript	c.647C>T	p.Pro216Leu	missense_variant	6/10			P1	C9JRZ8-1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000207

AC:

AN:

245864

Hom.:

AF XY:

0.000211

AC XY:

AN XY:

132956

show subpopulations

Gnomad AFR exome

AF:

0.000375

Gnomad AMR exome

AF:

0.0000596

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000554

Gnomad SAS exome

AF:

0.000839

Gnomad FIN exome

AF:

0.000140

Gnomad NFE exome

AF:

0.000108

Gnomad OTH exome

AF:

0.000335

GnomAD4 exome

AF:

0.000118

AC:

173

AN:

1461270

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

726940

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00102

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.0000261

Gnomad4 OTH exome

AF:

0.000530

GnomAD4 genome

AF:

0.000138

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000144

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.000272

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

Mar 29, 2024

The c.731C>T (p.P244L) alteration is located in exon 8 (coding exon 6) of the AKR1B15 gene. This alteration results from a C to T substitution at nucleotide position 731, causing the proline (P) at amino acid position 244 to be replaced by a leucine (L). 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

-0.31

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.71

.;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-7.3

D;.

REVEL

Benign

0.23

Sift

Uncertain

0.0090

D;.

Sift4G

Uncertain

0.049

D;D

Vest4

0.52

MVP

0.25

MPC

0.14

ClinPred

0.15

GERP RS

3.9

gMVP

0.50

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