NM_144683.4:c.697G>A

Variant names:

• chr17-28898878-C-T
• rs887243259
• NM_144683.4:c.697G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_144683.4(DHRS13):​c.697G>A​(p.Glu233Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: DHRS13 NM_144683.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.75
• Publications: 1 publications found

Genes affected

DHRS13 (HGNC:28326): (dehydrogenase/reductase 13) Predicted to enable NADP-retinol dehydrogenase activity. Predicted to be involved in retinal metabolic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000266642 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36694127).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144683.4. 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
	DHRS13	NM_144683.4	MANE Select	c.697G>A	p.Glu233Lys	missense	Exon 5 of 5	NP_653284.2	Q6UX07-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHRS13	ENST00000378895.9	TSL:1 MANE Select	c.697G>A	p.Glu233Lys	missense	Exon 5 of 5	ENSP00000368173.4	Q6UX07-1
	DHRS13	ENST00000394901.7	TSL:1	c.547G>A	p.Glu183Lys	missense	Exon 4 of 4	ENSP00000378361.3	Q6UX07-2
	DHRS13	ENST00000913592.1		c.694G>A	p.Glu232Lys	missense	Exon 5 of 5	ENSP00000583651.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152144 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152144 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74334

African (AFR) AF: 0.00 AC: 0 AN: 41412

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.37	T
MetaSVM	Uncertain	0.36	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.7
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.044	D
Polyphen		0.68	P
Vest4		0.40
MVP		0.73
MPC		0.43
ClinPred		0.96	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.70

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: rs887243259; hg19: chr17-27225896;