14-60150123-C-T

Variant names:

• chr14-60150123-C-T
• rs754937578
• NM_016029.4:c.698G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016029.4(DHRS7):​c.698G>A​(p.Cys233Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,434,048 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. C233S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: DHRS7 NM_016029.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.919
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.698G>A	p.Cys233Tyr	missense	Exon 5 of 7	NP_057113.1	Q9Y394-1
	DHRS7	NM_001322280.2		c.548G>A	p.Cys183Tyr	missense	Exon 5 of 7	NP_001309209.1	Q9Y394-2
	DHRS7	NM_001322282.2		c.458G>A	p.Cys153Tyr	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.698G>A	p.Cys233Tyr	missense	Exon 5 of 7	ENSP00000451882.1	Q9Y394-1
	DHRS7	ENST00000536410.6	TSL:1	c.548G>A	p.Cys183Tyr	missense	Exon 5 of 7	ENSP00000442993.2	Q9Y394-2
	DHRS7	ENST00000554101.5	TSL:2	c.680G>A	p.Cys227Tyr	missense	Exon 5 of 6	ENSP00000450899.1	H0YJ66

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1434048 Hom.: 0 Cov.: 32 AF XY: 0.00000140 AC XY: 1 AN XY: 713276

African (AFR) AF: 0.0000314 AC: 1 AN: 31836

American (AMR) AF: 0.00 AC: 0 AN: 42912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25088

East Asian (EAS) AF: 0.00 AC: 0 AN: 37060

South Asian (SAS) AF: 0.00 AC: 0 AN: 83710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5600

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097234

Other (OTH) AF: 0.00 AC: 0 AN: 58534

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Uncertain	0.53	D
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.41
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.92
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-8.8	D
REVEL	Uncertain	0.30
Sift	Benign	0.15	T
Sift4G	Uncertain	0.042	D
Polyphen		0.058	B
Vest4		0.34
MutPred		0.63		Gain of catalytic residue at I232 (P = 0.0344)
MVP		0.42
MPC		0.069
ClinPred		0.70	D
GERP RS		0.0035
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.77
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs754937578; hg19: chr14-60616841;