NM_001040177.3:c.60C>A

Variant names:

• chr10-4830695-C-A
• rs3750739
• NM_001040177.3:c.60C>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001040177.3(AKR1E2):​c.60C>A​(p.Thr20Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0426 in 1,613,746 control chromosomes in the GnomAD database, including 1,820 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (149 hom., cov: 32)
  • Exomes 𝑓: 0.043 (1671 hom.)
• Consequence: AKR1E2 NM_001040177.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.15
• Publications: 11 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-4830695-C-A is Benign according to our data. Variant chr10-4830695-C-A is described in ClinVar as Benign. ClinVar VariationId is 1225519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.15 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

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.60C>A	p.Thr20Thr	synonymous	Exon 2 of 10	NP_001035267.1	Q96JD6-1
	AKR1E2	NM_001271021.2		c.60C>A	p.Thr20Thr	synonymous	Exon 2 of 8	NP_001257950.1	Q96JD6-2
	AKR1E2	NM_001271025.2		c.60C>A	p.Thr20Thr	synonymous	Exon 2 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.60C>A	p.Thr20Thr	synonymous	Exon 2 of 10	ENSP00000298375.7	Q96JD6-1
	AKR1E2	ENST00000334019.4	TSL:1	c.60C>A	p.Thr20Thr	synonymous	Exon 2 of 8	ENSP00000335034.4	Q96JD6-2
	AKR1E2	ENST00000532248.5	TSL:1	c.60C>A	p.Thr20Thr	synonymous	Exon 2 of 7	ENSP00000432947.1	Q96JD6-3

Frequencies

GnomAD3 genomes AF: 0.0349 AC: 5305 AN: 152018 Hom.: 149 Cov.: 32

Gnomad AFR AF: 0.00986

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0218

Gnomad FIN AF: 0.0154

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0496

Gnomad OTH AF: 0.0374

GnomAD2 exomes AF: 0.0400 AC: 10043 AN: 251332 AF XY: 0.0396

Gnomad AFR exome AF: 0.00886

Gnomad AMR exome AF: 0.0317

Gnomad ASJ exome AF: 0.0164

Gnomad EAS exome AF: 0.119

Gnomad FIN exome AF: 0.0148

Gnomad NFE exome AF: 0.0475

Gnomad OTH exome AF: 0.0341

GnomAD4 exome AF: 0.0434 AC: 63379 AN: 1461610 Hom.: 1671 Cov.: 30 AF XY: 0.0429 AC XY: 31179 AN XY: 727116

African (AFR) AF: 0.00711 AC: 238 AN: 33478

American (AMR) AF: 0.0316 AC: 1413 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0155 AC: 404 AN: 26130

East Asian (EAS) AF: 0.124 AC: 4935 AN: 39692

South Asian (SAS) AF: 0.0171 AC: 1473 AN: 86242

European-Finnish (FIN) AF: 0.0172 AC: 917 AN: 53408

Middle Eastern (MID) AF: 0.0128 AC: 74 AN: 5768

European-Non Finnish (NFE) AF: 0.0465 AC: 51722 AN: 1111780

Other (OTH) AF: 0.0365 AC: 2203 AN: 60394

GnomAD4 genome AF: 0.0349 AC: 5302 AN: 152136 Hom.: 149 Cov.: 32 AF XY: 0.0332 AC XY: 2469 AN XY: 74402

African (AFR) AF: 0.00983 AC: 408 AN: 41492

American (AMR) AF: 0.0348 AC: 532 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3468

East Asian (EAS) AF: 0.114 AC: 587 AN: 5154

South Asian (SAS) AF: 0.0218 AC: 105 AN: 4818

European-Finnish (FIN) AF: 0.0154 AC: 163 AN: 10596

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0496 AC: 3373 AN: 68002

Other (OTH) AF: 0.0374 AC: 79 AN: 2110

Alfa AF: 0.0312 Hom.: 32

Bravo AF: 0.0361

EpiCase AF: 0.0459

EpiControl AF: 0.0484

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.016
DANN	Benign	0.52
PhyloP100		-5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3750739; hg19: chr10-4872887; COSMIC: COSV53629763; COSMIC: COSV53629763;