14-60153070-A-T

Variant names:

• chr14-60153070-A-T
• NM_016029.4:c.502T>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016029.4(DHRS7):​c.502T>A​(p.Ser168Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DHRS7 NM_016029.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.11

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.818

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHRS7	NM_016029.4	c.502T>A	p.Ser168Thr	missense_variant	Exon 4 of 7	ENST00000557185.6	NP_057113.1
DHRS7	NM_001322280.2	c.352T>A	p.Ser118Thr	missense_variant	Exon 4 of 7		NP_001309209.1
DHRS7	NM_001322281.2	c.82T>A	p.Ser28Thr	missense_variant	Exon 4 of 7		NP_001309210.1
DHRS7	NM_001322282.2	c.393+889T>A		intron_variant	Intron 3 of 5		NP_001309211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHRS7	ENST00000557185.6	c.502T>A	p.Ser168Thr	missense_variant	Exon 4 of 7	1	NM_016029.4	ENSP00000451882.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 12, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.502T>A (p.S168T) alteration is located in exon 4 (coding exon 4) of the DHRS7 gene. This alteration results from a T to A substitution at nucleotide position 502, causing the serine (S) at amino acid position 168 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T;T;T;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	.;D;.;T
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.82	D;D;D;D
MetaSVM	Uncertain	0.12	D
MutationAssessor	Benign	0.15	N;N;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.7	D;D;.;D
REVEL	Pathogenic	0.67
Sift	Uncertain	0.018	D;D;.;D
Sift4G	Uncertain	0.031	D;D;T;D
Polyphen		1.0	D;D;.;.
Vest4		0.72
MutPred		0.61		Loss of ubiquitination at K171 (P = 0.3061);Loss of ubiquitination at K171 (P = 0.3061);Loss of ubiquitination at K171 (P = 0.3061);.;
MVP		0.99
MPC		0.30
ClinPred		0.99	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.53
gMVP		0.67

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: chr14-60619788;