chr14-60153037-C-G

Variant names:

• chr14-60153037-C-G
• rs146061320
• NM_016029.4:c.535G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016029.4(DHRS7):​c.535G>C​(p.Glu179Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. E179K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DHRS7 NM_016029.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16926968).

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.535G>C	p.Glu179Gln	missense	Exon 4 of 7	NP_057113.1	Q9Y394-1
	DHRS7	NM_001322280.2		c.385G>C	p.Glu129Gln	missense	Exon 4 of 7	NP_001309209.1	Q9Y394-2
	DHRS7	NM_001322281.2		c.115G>C	p.Glu39Gln	missense	Exon 4 of 7	NP_001309210.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHRS7	ENST00000557185.6	TSL:1 MANE Select	c.535G>C	p.Glu179Gln	missense	Exon 4 of 7	ENSP00000451882.1	Q9Y394-1
	DHRS7	ENST00000536410.6	TSL:1	c.385G>C	p.Glu129Gln	missense	Exon 4 of 7	ENSP00000442993.2	Q9Y394-2
	DHRS7	ENST00000554101.5	TSL:2	c.517G>C	p.Glu173Gln	missense	Exon 4 of 6	ENSP00000450899.1	H0YJ66

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461880 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.029
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.7
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.074
Sift	Benign	0.42	T
Sift4G	Benign	0.54	T
Polyphen		0.76	P
Vest4		0.14
MutPred		0.38		Gain of MoRF binding (P = 0.0578)
MVP		0.66
MPC		0.11
ClinPred		0.64	D
GERP RS		3.6
PromoterAI		-0.024	Neutral
Varity_R		0.054
gMVP		0.48
Mutation Taster		=87/13	polymorphism

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: rs146061320; hg19: chr14-60619755;