NM_001040177.3:c.34T>A

Variant names:

• chr10-4826358-T-A
• NM_001040177.3:c.34T>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001040177.3(AKR1E2):​c.34T>A​(p.Trp12Arg) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AKR1E2 NM_001040177.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.47
• Publications: 0 publications found

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]

AKR1E2 Gene-Disease associations (from GenCC):

• cataract

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.914

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040177.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1E2	NM_001040177.3	MANE Select	c.34T>A	p.Trp12Arg	missense	Exon 1 of 10	NP_001035267.1	Q96JD6-1
	AKR1E2	NM_001271021.2		c.34T>A	p.Trp12Arg	missense	Exon 1 of 8	NP_001257950.1	Q96JD6-2
	AKR1E2	NM_001271025.2		c.34T>A	p.Trp12Arg	missense	Exon 1 of 7	NP_001257954.1	Q96JD6-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1E2	ENST00000298375.12	TSL:1 MANE Select	c.34T>A	p.Trp12Arg	missense	Exon 1 of 10	ENSP00000298375.7	Q96JD6-1
	AKR1E2	ENST00000334019.4	TSL:1	c.34T>A	p.Trp12Arg	missense	Exon 1 of 8	ENSP00000335034.4	Q96JD6-2
	AKR1E2	ENST00000532248.5	TSL:1	c.34T>A	p.Trp12Arg	missense	Exon 1 of 7	ENSP00000432947.1	Q96JD6-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.090	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.078
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		1.5
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-11	D
REVEL	Benign	0.25
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.012	D
Polyphen		0.94	P
Vest4		0.66
MutPred		0.76		Gain of disorder (P = 0.003)
MVP		0.34
MPC		0.56
ClinPred		1.0	D
GERP RS		2.8
PromoterAI		0.18	Neutral
Varity_R		0.86
gMVP		0.90
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr10-4868550;