14-60149495-A-G

Position:

• chr14-60149495-A-G

Variant summary

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

The NM_016029.4(DHRS7):​c.830T>C​(p.Met277Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DHRS7 NM_016029.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.53

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]

DHRS7 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHRS7	NM_016029.4	c.830T>C	p.Met277Thr	missense_variant	6/7	ENST00000557185.6	NP_057113.1
DHRS7	NM_001322280.2	c.680T>C	p.Met227Thr	missense_variant	6/7		NP_001309209.1
DHRS7	NM_001322282.2	c.590T>C	p.Met197Thr	missense_variant	5/6		NP_001309211.1
DHRS7	NM_001322281.2	c.410T>C	p.Met137Thr	missense_variant	6/7		NP_001309210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHRS7	ENST00000557185.6	c.830T>C	p.Met277Thr	missense_variant	6/7	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2024

The c.830T>C (p.M277T) alteration is located in exon 6 (coding exon 6) of the DHRS7 gene. This alteration results from a T to C substitution at nucleotide position 830, causing the methionine (M) at amino acid position 277 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	Uncertain	0.36
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.085	T;T;T;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.74	.;T;.;T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.44	T;T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.6	M;M;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.7	D;D;.;D
REVEL	Benign	0.16
Sift	Benign	0.055	T;T;.;T
Sift4G	Benign	0.077	T;T;T;T
Polyphen		0.030	B;B;.;.
Vest4		0.34
MutPred		0.73		Loss of stability (P = 0.0104);Loss of stability (P = 0.0104);Loss of stability (P = 0.0104);.;
MVP		0.75
MPC		0.050
ClinPred		0.95	D
GERP RS		5.7
Varity_R		0.27
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr14-60616213;