Variant 7-134568158-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001080538.3(AKR1B15):c.151T>C(p.Ser51Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,072 control chromosomes in the GnomAD database, with no homozygous occurrence. 15/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Consequence

AKR1B15
NM_001080538.3 missense, splice_region

Scores

Splicing: ADA: 0.001387

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72

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:

AKR1B15 (HGNC:):

AKR1B15 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKR1B15	NM_001080538.3 linkuse as main transcript	c.151T>C	p.Ser51Pro	missense_variant, splice_region_variant	4/12	ENST00000457545.7	NP_001074007.2	C9JRZ8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AKR1B15	ENST00000457545.7 linkuse as main transcript	c.151T>C	p.Ser51Pro	missense_variant, splice_region_variant	4/12	5	NM_001080538.3	ENSP00000389289.1	C9JRZ8-2
AKR1B15	ENST00000467156.1 linkuse as main transcript	n.760T>C		splice_region_variant, non_coding_transcript_exon_variant	2/3	1
AKR1B15	ENST00000423958.2 linkuse as main transcript	c.151T>C	p.Ser51Pro	missense_variant, splice_region_variant	2/10	5		ENSP00000397009.2	C9JRZ8-2
AKR1B15	ENST00000652743.1 linkuse as main transcript	c.67T>C	p.Ser23Pro	missense_variant, splice_region_variant	2/10			ENSP00000498877.1	C9JRZ8-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

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

Cov.:

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152072

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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 14, 2024

The c.151T>C (p.S51P) alteration is located in exon 4 (coding exon 2) of the AKR1B15 gene. This alteration results from a T to C substitution at nucleotide position 151, causing the serine (S) at amino acid position 51 to be replaced by a proline (P). 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

0.32

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.043

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.20

.;T

M_CAP

Benign

0.036

MetaRNN

Uncertain

0.71

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

1.4

N;.

REVEL

Benign

0.13

Sift

Uncertain

0.0030

D;.

Sift4G

Benign

0.077

T;T

Vest4

0.71

MutPred

0.51

Loss of stability (P = 0.0609);Loss of stability (P = 0.0609);

MVP

0.24

MPC

0.18

ClinPred

0.76

GERP RS

2.7

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0014

dbscSNV1_RF

Benign

0.048

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