7-134568271-A-T

Position:

• chr7-134568271-A-T

Variant summary

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

The NM_001080538.3(AKR1B15):​c.264A>T​(p.Gln88His) 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: -2.53

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=0.08027148).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKR1B15	NM_001080538.3	c.264A>T	p.Gln88His	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.264A>T	p.Gln88His	missense_variant	4/12	5	NM_001080538.3	ENSP00000389289.1
AKR1B15	ENST00000467156.1	n.873A>T		non_coding_transcript_exon_variant	2/3	1
AKR1B15	ENST00000423958.2	c.264A>T	p.Gln88His	missense_variant	2/10	5		ENSP00000397009.2
AKR1B15	ENST00000652743.1	c.180A>T	p.Gln60His	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

Sep 30, 2024

The c.264A>T (p.Q88H) alteration is located in exon 4 (coding exon 2) of the AKR1B15 gene. This alteration results from a A to T substitution at nucleotide position 264, causing the glutamine (Q) at amino acid position 88 to be replaced by a histidine (H). 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	0.21
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.91
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.85	.;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.080	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.60	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.7	D;.
REVEL	Benign	0.018
Sift	Benign	0.042	D;.
Sift4G	Benign	0.066	T;T
Vest4		0.20
MutPred		0.49		Gain of ubiquitination at K90 (P = 0.1047);Gain of ubiquitination at K90 (P = 0.1047);
MVP		0.040
MPC		0.26
ClinPred		0.11	T
GERP RS		-2.2
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr7-134253023;