NM_198083.4:c.16C>A

Variant names:

• chr14-23988963-C-A
• NM_198083.4:c.16C>A

Variant summary

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

The NM_198083.4(DHRS4L2):​c.16C>A​(p.Leu6Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,460,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L6V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: DHRS4L2 NM_198083.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294

Genes affected

DHRS4L2 (HGNC:19731): (dehydrogenase/reductase 4 like 2) This gene encodes a member of the short chain dehydrogenase reductase family. The encoded protein may be an NADPH dependent retinol oxidoreductase. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2010]

DHRS4-AS1 (HGNC:23175): (DHRS4 antisense RNA 1)

DHRS4L1 (HGNC:):

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=0.1539183).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHRS4L2	NM_198083.4	c.16C>A	p.Leu6Met	missense_variant	Exon 1 of 8	ENST00000335125.11	NP_932349.2
DHRS4L2	NM_001193635.1	c.45-1219C>A		intron_variant	Intron 3 of 8		NP_001180564.1
DHRS4L2	NM_001193636.1	c.-175-1219C>A		intron_variant	Intron 1 of 7		NP_001180565.1
DHRS4L2	NM_001193637.1	c.-175-1219C>A		intron_variant	Intron 1 of 5		NP_001180566.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHRS4L2	ENST00000335125.11	c.16C>A	p.Leu6Met	missense_variant	Exon 1 of 8	1	NM_198083.4	ENSP00000334801.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1460226 Hom.: 0 Cov.: 34 AF XY: 0.0000138 AC XY: 10 AN XY: 726328

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.0048	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T;T;.;.;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.29	T;T;.;.;T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.15	T;T;T;T;T
MetaSVM	Benign	-0.48	T
PROVEAN	Benign	-0.27	N;N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.055	T;D;D;T;T
Sift4G	Benign	0.087	T;T;T;T;T
Polyphen		0.97	.;.;.;D;D
Vest4		0.23
MVP		0.82
MPC		0.18
ClinPred		0.35	T
GERP RS		-0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-24458172;