1-12611319-A-T

Position:

• chr1-12611319-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000616661.5(DHRS3):​c.195+5835T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)
• Consequence: DHRS3 ENST00000616661.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.968

Genes affected

DHRS3 (HGNC:17693): (dehydrogenase/reductase 3) Predicted to enable NAD-retinol dehydrogenase activity. Predicted to be involved in regulation of retinoic acid receptor signaling pathway and retinoid metabolic process. Predicted to act upstream of or within several processes, including animal organ morphogenesis; negative regulation of retinoic acid receptor signaling pathway; and regulation of ossification. Predicted to be located in endoplasmic reticulum membrane and photoreceptor outer segment membrane. Predicted to be active in lipid droplet. [provided by Alliance of Genome Resources, Apr 2022]

DHRS3 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHRS3	NM_004753.7	c.195+5835T>A		intron_variant		ENST00000616661.5	NP_004744.2
DHRS3	XM_047434406.1	c.-10944T>A		5_prime_UTR_variant	1/6		XP_047290362.1
DHRS3	NM_001319225.2	c.-61+5241T>A		intron_variant			NP_001306154.1
DHRS3	XM_006711036.3	c.195+5835T>A		intron_variant			XP_006711099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHRS3	ENST00000616661.5	c.195+5835T>A		intron_variant		1	NM_004753.7	ENSP00000480439.1
DHRS3	ENST00000464917.5	c.-61+5241T>A		intron_variant		3		ENSP00000478218.1
DHRS3	ENST00000482265.1	n.137+5241T>A		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.19

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

Publications

LitVar

Other links and lift over

dbSNP: rs4618985; hg19: chr1-12671324;