NM_001040177.3:c.19G>A

Variant names:

• chr10-4826343-G-A
• rs1588423019
• NM_001040177.3:c.19G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001040177.3(AKR1E2):​c.19G>A​(p.Val7Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000554 in 1,082,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: AKR1E2 NM_001040177.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.982

Genes affected

AKR1E2 (HGNC:23437): (aldo-keto reductase family 1 member E2) The protein encoded by this gene is a member of the aldo-keto reductase superfamily. Members in this family are characterized by their structure (evolutionarily highly conserved TIM barrel) and function (NAD(P)H-dependent oxido-reduction of carbonyl groups). Transcripts of this gene have been reported in specimens of human testis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39285246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1E2	NM_001040177.3	c.19G>A	p.Val7Met	missense_variant	Exon 1 of 10	ENST00000298375.12	NP_001035267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1E2	ENST00000298375.12	c.19G>A	p.Val7Met	missense_variant	Exon 1 of 10	1	NM_001040177.3	ENSP00000298375.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000554 AC: 6 AN: 1082706 Hom.: 0 Cov.: 32 AF XY: 0.00000391 AC XY: 2 AN XY: 511536

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000435

Gnomad4 OTH exome AF: 0.0000229

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0055	T;.;.;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.12	N
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.39	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L;L;L
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.98	N;N;N;N
REVEL	Benign	0.10
Sift	Uncertain	0.017	D;D;D;D
Sift4G	Uncertain	0.032	D;D;D;D
Polyphen		0.99	D;D;P;D
Vest4		0.23
MutPred		0.69		Gain of disorder (P = 0.0478);Gain of disorder (P = 0.0478);Gain of disorder (P = 0.0478);Gain of disorder (P = 0.0478);
MVP		0.067
MPC		0.38
ClinPred		0.62	D
GERP RS		-4.2
Varity_R		0.27
gMVP		0.65

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

LitVar

Other links and lift over

dbSNP: rs1588423019; hg19: chr10-4868535;