chr7-134576999-G-T

Position:

• chr7-134576999-G-T

Variant summary

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

The NM_001080538.3(AKR1B15):​c.862G>T​(p.Val288Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AKR1B15 NM_001080538.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.63

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]

ACMG classification

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	UniProt
AKR1B15	NM_001080538.3	c.862G>T	p.Val288Leu	missense_variant	10/12	ENST00000457545.7
AKR1B15	NM_001367820.1	c.862G>T	p.Val288Leu	missense_variant	9/11
AKR1B15	NM_001367821.1	c.778G>T	p.Val260Leu	missense_variant	9/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1B15	ENST00000457545.7	c.862G>T	p.Val288Leu	missense_variant	10/12	5	NM_001080538.3
AKR1B15	ENST00000423958.2	c.862G>T	p.Val288Leu	missense_variant	8/10	5
AKR1B15	ENST00000652743.1	c.778G>T	p.Val260Leu	missense_variant	8/10			P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

May 09, 2023

The c.862G>T (p.V288L) alteration is located in exon 10 (coding exon 8) of the AKR1B15 gene. This alteration results from a G to T substitution at nucleotide position 862, causing the valine (V) at amino acid position 288 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	Pathogenic	0.64
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.90
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.55
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	.;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	0.86	D;D
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.7	D;.
REVEL	Benign	0.15
Sift	Uncertain	0.0060	D;.
Sift4G	Uncertain	0.0060	D;D
Vest4		0.48
MutPred		0.76		Loss of MoRF binding (P = 0.1062);Loss of MoRF binding (P = 0.1062);
MVP		0.19
MPC		0.044
ClinPred		0.23	T
GERP RS		2.6
gMVP		0.35

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: chr7-134261751;