chr14-60149556-T-C

Position:

• chr14-60149556-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016029.4(DHRS7):​c.769A>G​(p.Asn257Asp) 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. 16/21 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: -1.45

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039975822).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHRS7	NM_016029.4	c.769A>G	p.Asn257Asp	missense_variant	6/7	ENST00000557185.6	NP_057113.1
DHRS7	NM_001322280.2	c.619A>G	p.Asn207Asp	missense_variant	6/7		NP_001309209.1
DHRS7	NM_001322282.2	c.529A>G	p.Asn177Asp	missense_variant	5/6		NP_001309211.1
DHRS7	NM_001322281.2	c.349A>G	p.Asn117Asp	missense_variant	6/7		NP_001309210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHRS7	ENST00000557185.6	c.769A>G	p.Asn257Asp	missense_variant	6/7	1	NM_016029.4	ENSP00000451882	P1

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

Oct 17, 2023

The c.769A>G (p.N257D) alteration is located in exon 6 (coding exon 6) of the DHRS7 gene. This alteration results from a A to G substitution at nucleotide position 769, causing the asparagine (N) at amino acid position 257 to be replaced by an aspartic acid (D). 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	0.082
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.014
DANN	Benign	0.28
DEOGEN2	Benign	0.0039	T;T;T;.
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.27	.;T;.;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.040	T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	-1.1	N;N;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.020	N;N;.;N
REVEL	Benign	0.24
Sift	Benign	0.70	T;T;.;T
Sift4G	Benign	0.73	T;T;T;T
Polyphen		0.0	B;B;.;.
Vest4		0.12
MutPred		0.29		Loss of MoRF binding (P = 0.0898);Loss of MoRF binding (P = 0.0898);Loss of MoRF binding (P = 0.0898);.;
MVP		0.79
MPC		0.047
ClinPred		0.030	T
GERP RS		-11
Varity_R		0.034
gMVP		0.24

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: chr14-60616274;