NM_016029.4:c.649C>T

Variant names:

• chr14-60150172-G-A
• rs1427986469
• NM_016029.4:c.649C>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_016029.4(DHRS7):​c.649C>T​(p.Leu217Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000402 in 1,491,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000021 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000042 (0 hom.)
• Consequence: DHRS7 NM_016029.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.30
• Publications: 2 publications found

Genes affected

DHRS7 (HGNC:21524): (dehydrogenase/reductase 7) This gene encodes a member of the short-chain dehydrogenases/reductases (SDR) family, which has over 46,000 members. Members in this family are enzymes that metabolize many different compounds, such as steroid hormones, prostaglandins, retinoids, lipids and xenobiotics. [provided by RefSeq, Apr 2016]

PCNX4 (HGNC:20349): (pecanex 4) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.979

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016029.4. 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
	DHRS7	NM_016029.4	MANE Select	c.649C>T	p.Leu217Phe	missense	Exon 5 of 7	NP_057113.1	Q9Y394-1
	DHRS7	NM_001322280.2		c.499C>T	p.Leu167Phe	missense	Exon 5 of 7	NP_001309209.1	Q9Y394-2
	DHRS7	NM_001322282.2		c.409C>T	p.Leu137Phe	missense	Exon 4 of 6	NP_001309211.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHRS7	ENST00000557185.6	TSL:1 MANE Select	c.649C>T	p.Leu217Phe	missense	Exon 5 of 7	ENSP00000451882.1	Q9Y394-1
	DHRS7	ENST00000536410.6	TSL:1	c.499C>T	p.Leu167Phe	missense	Exon 5 of 7	ENSP00000442993.2	Q9Y394-2
	DHRS7	ENST00000554101.5	TSL:2	c.631C>T	p.Leu211Phe	missense	Exon 5 of 6	ENSP00000450899.1	H0YJ66

Frequencies

GnomAD3 genomes AF: 0.0000213 AC: 3 AN: 140610 Hom.: 0 Cov.: 30

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: 0.0000449

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000537 AC: 1 AN: 186058 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000107

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000422 AC: 57 AN: 1351208 Hom.: 0 Cov.: 32 AF XY: 0.0000329 AC XY: 22 AN XY: 668482

African (AFR) AF: 0.00 AC: 0 AN: 27894

American (AMR) AF: 0.00 AC: 0 AN: 30340

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22394

East Asian (EAS) AF: 0.00 AC: 0 AN: 35348

South Asian (SAS) AF: 0.0000157 AC: 1 AN: 63740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50166

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5306

European-Non Finnish (NFE) AF: 0.0000509 AC: 54 AN: 1060954

Other (OTH) AF: 0.0000363 AC: 2 AN: 55066

GnomAD4 genome AF: 0.0000213 AC: 3 AN: 140610 Hom.: 0 Cov.: 30 AF XY: 0.0000147 AC XY: 1 AN XY: 67928

African (AFR) AF: 0.00 AC: 0 AN: 35152

American (AMR) AF: 0.00 AC: 0 AN: 14066

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3420

East Asian (EAS) AF: 0.00 AC: 0 AN: 4788

South Asian (SAS) AF: 0.00 AC: 0 AN: 4466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000449 AC: 3 AN: 66758

Other (OTH) AF: 0.00 AC: 0 AN: 1910

Alfa AF: 0.0000247 Hom.: 0

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	Uncertain	0.41
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	D
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.072	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Pathogenic	0.86	D
MutationAssessor	Pathogenic	2.9	M
PhyloP100		6.3
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.7	D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.036	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.81		Loss of stability (P = 0.0948)
MVP		1.0
MPC		0.31
ClinPred		0.97	D
GERP RS		5.2
Varity_R		0.48
gMVP		0.85
Mutation Taster		=17/83	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1427986469; hg19: chr14-60616890;