7-134568266-A-G

Position:

• chr7-134568266-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080538.3(AKR1B15):​c.259A>G​(p.Ile87Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AKR1B15 NM_001080538.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.745

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 (HGNC:):

ACMG classification

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=0.116888225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKR1B15	NM_001080538.3	c.259A>G	p.Ile87Val	missense_variant	4/12	ENST00000457545.7	NP_001074007.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKR1B15	ENST00000457545.7	c.259A>G	p.Ile87Val	missense_variant	4/12	5	NM_001080538.3	ENSP00000389289.1
AKR1B15	ENST00000467156.1	n.868A>G		non_coding_transcript_exon_variant	2/3	1
AKR1B15	ENST00000423958.2	c.259A>G	p.Ile87Val	missense_variant	2/10	5		ENSP00000397009.2
AKR1B15	ENST00000652743.1	c.175A>G	p.Ile59Val	missense_variant	2/10			ENSP00000498877.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 05, 2024

The c.259A>G (p.I87V) alteration is located in exon 4 (coding exon 2) of the AKR1B15 gene. This alteration results from a A to G substitution at nucleotide position 259, causing the isoleucine (I) at amino acid position 87 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	0.16
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Uncertain	0.98
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.12	N
LIST_S2	Uncertain	0.89	.;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L;L
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.80	N;.
REVEL	Benign	0.036
Sift	Benign	0.053	T;.
Sift4G	Benign	0.11	T;T
Vest4		0.16
MutPred		0.64		Gain of ubiquitination at K90 (P = 0.0898);Gain of ubiquitination at K90 (P = 0.0898);
MVP		0.10
MPC		0.22
ClinPred		0.20	T
GERP RS		3.0
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-134253018;