10-4830807-G-C

Variant names:

• chr10-4830807-G-C
• NM_001040177.3:c.172G>C

Variant summary

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

The NM_001040177.3(AKR1E2):​c.172G>C​(p.Ala58Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 6.8e-7 (0 hom.)
• Consequence: AKR1E2 NM_001040177.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2481493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1E2	NM_001040177.3	c.172G>C	p.Ala58Pro	missense_variant	Exon 2 of 10	ENST00000298375.12	NP_001035267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1E2	ENST00000298375.12	c.172G>C	p.Ala58Pro	missense_variant	Exon 2 of 10	1	NM_001040177.3	ENSP00000298375.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461854 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727226

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.032	T;T;.;.;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.28	T;T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.25	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.22	.;N;N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.2	D;D;D;D;D
REVEL	Benign	0.072
Sift	Uncertain	0.011	D;D;D;T;D
Sift4G	Uncertain	0.035	D;D;D;D;D
Polyphen		0.94, 0.013, 0.73, 0.93	.;P;B;P;P
Vest4		0.23, 0.27, 0.23, 0.27
MutPred		0.48		.;Loss of MoRF binding (P = 0.0731);Loss of MoRF binding (P = 0.0731);Loss of MoRF binding (P = 0.0731);Loss of MoRF binding (P = 0.0731);
MVP		0.22
MPC		0.43
ClinPred		0.58	D
GERP RS		-1.4
Varity_R		0.45
gMVP		0.75

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: chr10-4872999;