14-60153981-G-A

Position:

• chr14-60153981-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016029.4(DHRS7):​c.371C>T​(p.Ala124Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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: 0.413

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13657117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHRS7	NM_016029.4	c.371C>T	p.Ala124Val	missense_variant	3/7	ENST00000557185.6
DHRS7	NM_001322280.2	c.221C>T	p.Ala74Val	missense_variant	3/7
DHRS7	NM_001322282.2	c.371C>T	p.Ala124Val	missense_variant	3/6
DHRS7	NM_001322281.2	c.-57C>T		5_prime_UTR_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHRS7	ENST00000557185.6	c.371C>T	p.Ala124Val	missense_variant	3/7	1	NM_016029.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Oct 05, 2023

The c.371C>T (p.A124V) alteration is located in exon 3 (coding exon 3) of the DHRS7 gene. This alteration results from a C to T substitution at nucleotide position 371, causing the alanine (A) at amino acid position 124 to be replaced by a valine (V). 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	0.096
BayesDel_addAF	Benign	-0.0069	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.33	T;T;T;.
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.66	.;T;.;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.6	L;L;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-2.0	N;N;.;N
REVEL	Benign	0.13
Sift	Benign	0.20	T;T;.;T
Sift4G	Benign	0.30	T;T;T;T
Polyphen		0.019	B;B;.;.
Vest4		0.11
MutPred		0.50		Gain of methylation at K123 (P = 0.0979);Gain of methylation at K123 (P = 0.0979);Gain of methylation at K123 (P = 0.0979);.;
MVP		0.92
MPC		0.047
ClinPred		0.14	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.047
gMVP		0.39

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-60620699;