chr17-21188782-G-A

Position:

• chr17-21188782-G-A

Variant summary

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

The NM_015510.5(DHRS7B):​c.691G>A​(p.Glu231Lys) 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: DHRS7B NM_015510.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.878

Genes affected

DHRS7B (HGNC:24547): (dehydrogenase/reductase 7B) Predicted to enable DNA-binding transcription factor binding activity and transcription corepressor activity. Predicted to be involved in neutrophil differentiation. Predicted to act upstream of or within several processes, including brown fat cell differentiation; phosphatidylcholine biosynthetic process; and regulation of cold-induced thermogenesis. Located in 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=0.07268104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHRS7B	NM_015510.5	c.691G>A	p.Glu231Lys	missense_variant	6/7	ENST00000395511.8	NP_056325.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHRS7B	ENST00000395511.8	c.691G>A	p.Glu231Lys	missense_variant	6/7	1	NM_015510.5	ENSP00000378887	A1

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

Feb 02, 2022

The c.691G>A (p.E231K) alteration is located in exon 6 (coding exon 6) of the DHRS7B gene. This alteration results from a G to A substitution at nucleotide position 691, causing the glutamic acid (E) at amino acid position 231 to be replaced by a lysine (K). 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	0.12
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	9.4
DANN	Benign	0.97
DEOGEN2	Benign	0.16	T;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.84	T;T;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.073	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.035	N;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.25	N;.;.
REVEL	Benign	0.034
Sift	Benign	1.0	T;.;.
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0010	B;.;.
Vest4		0.26
MutPred		0.47		Gain of ubiquitination at E231 (P = 0.0388);.;.;
MVP		0.54
MPC		0.20
ClinPred		0.052	T
GERP RS		2.0
Varity_R		0.026
gMVP		0.71

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: chr17-21092095;