7-134569519-A-G

Variant summary

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

The NM_001080538.3(AKR1B15):ā€‹c.425A>Gā€‹(p.Gln142Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

AKR1B15
NM_001080538.3 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.351
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]

Genome browser will be placed here

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=0.13375682).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AKR1B15NM_001080538.3 linkuse as main transcriptc.425A>G p.Gln142Arg missense_variant 5/12 ENST00000457545.7 NP_001074007.2 C9JRZ8-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AKR1B15ENST00000457545.7 linkuse as main transcriptc.425A>G p.Gln142Arg missense_variant 5/125 NM_001080538.3 ENSP00000389289.1 C9JRZ8-2
AKR1B15ENST00000467156.1 linkuse as main transcriptn.1034A>G non_coding_transcript_exon_variant 3/31
AKR1B15ENST00000423958.2 linkuse as main transcriptc.425A>G p.Gln142Arg missense_variant 3/105 ENSP00000397009.2 C9JRZ8-2
AKR1B15ENST00000652743.1 linkuse as main transcriptc.341A>G p.Gln114Arg missense_variant 3/10 ENSP00000498877.1 C9JRZ8-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251262
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135790
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
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:
0.000163
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461726
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
727166
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000134
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000936
Hom.:
0
Bravo
AF:
0.0000340

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 submitterclinical testingAmbry GeneticsApr 01, 2024The c.425A>G (p.Q142R) alteration is located in exon 5 (coding exon 3) of the AKR1B15 gene. This alteration results from a A to G substitution at nucleotide position 425, causing the glutamine (Q) at amino acid position 142 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
Uncertain
0.36
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
1.5
DANN
Uncertain
1.0
Eigen
Benign
-0.47
Eigen_PC
Benign
-0.54
FATHMM_MKL
Benign
0.17
N
LIST_S2
Uncertain
0.88
.;D
M_CAP
Benign
0.0093
T
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.46
N;N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-1.5
N;.
REVEL
Benign
0.092
Sift
Uncertain
0.015
D;.
Sift4G
Benign
0.069
T;T
Vest4
0.26
MutPred
0.46
Loss of ubiquitination at K145 (P = 0.1664);Loss of ubiquitination at K145 (P = 0.1664);
MVP
0.12
MPC
0.27
ClinPred
0.31
T
GERP RS
1.4
gMVP
0.26

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.

Other links and lift over

dbSNP: rs1433256843; hg19: chr7-134254271; API