chr1-12611224-T-G

Variant names:

• chr1-12611224-T-G
• rs4394668
• NM_004753.7:c.195+5930A>C

Variant summary

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

The NM_004753.7(DHRS3):​c.195+5930A>C 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 NM_004753.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• craniosynostosis

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ENSG00000305650 (HGNC:):

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=-0.92).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004753.7. 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
	DHRS3	NM_004753.7	MANE Select	c.195+5930A>C		intron	N/A	NP_004744.2
	DHRS3	NM_001319225.2		c.-61+5336A>C		intron	N/A	NP_001306154.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHRS3	ENST00000616661.5	TSL:1 MANE Select	c.195+5930A>C		intron	N/A	ENSP00000480439.1
	DHRS3	ENST00000714544.1		c.150+5930A>C		intron	N/A	ENSP00000519785.1
	DHRS3	ENST00000714545.1		c.150+5930A>C		intron	N/A	ENSP00000519786.1

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

Alfa AF: 0.00 Hom.: 14757

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.36
PhyloP100		-1.3

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: rs4394668; hg19: chr1-12671229;