NM_001253908.2:c.85-2103A>C

Variant names:

• chr10-5094307-A-C
• rs3763676
• NM_001253908.2:c.85-2103A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001253908.2(AKR1C3):​c.85-2103A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 730,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 23)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: AKR1C3 NM_001253908.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499
• Publications: 0 publications found

Genes affected

AKR1C3 (HGNC:386): (aldo-keto reductase family 1 member C3) This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols by utilizing NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ), and the oxidation of 9alpha,11beta-PGF2 to PGD2. It may play an important role in the pathogenesis of allergic diseases such as asthma, and may also have a role in controlling cell growth and/or differentiation. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001253908.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1C3	NM_001253908.2		c.85-2103A>C		intron	N/A	NP_001240837.1
	AKR1C3	NM_003739.6	MANE Select	c.-138A>C		upstream_gene	N/A	NP_003730.4
	AKR1C3	NM_001253909.2		c.-138A>C		upstream_gene	N/A	NP_001240838.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1C3	ENST00000439082.7	TSL:5	c.85-2103A>C		intron	N/A	ENSP00000401327.3
	AKR1C3	ENST00000605149.5	TSL:2	c.16-2103A>C		intron	N/A	ENSP00000474882.1
	AKR1C3	ENST00000602997.5	TSL:3	c.16-2103A>C		intron	N/A	ENSP00000474188.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000137 AC: 1 AN: 730092 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 385180

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 18012

American (AMR) AF: 0.00 AC: 0 AN: 33446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17902

East Asian (EAS) AF: 0.00 AC: 0 AN: 26984

South Asian (SAS) AF: 0.00 AC: 0 AN: 70370

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35424

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2732

European-Non Finnish (NFE) AF: 0.00000203 AC: 1 AN: 491970

Other (OTH) AF: 0.00 AC: 0 AN: 33252

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.82
DANN	Benign	0.55
PhyloP100		-0.50
PromoterAI		0.18	Neutral

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: rs3763676; hg19: chr10-5136499;