17-21172123-G-C

Position:

• chr17-21172123-G-C

Variant summary

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

The NM_015510.5(DHRS7B):​c.126G>C​(p.Gln42His) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DHRS7B NM_015510.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.23

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 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
DHRS7B	NM_015510.5	c.126G>C	p.Gln42His	missense_variant	2/7	ENST00000395511.8	NP_056325.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHRS7B	ENST00000395511.8	c.126G>C	p.Gln42His	missense_variant	2/7	1	NM_015510.5	ENSP00000378887	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461814 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727202

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Jun 24, 2022

The c.126G>C (p.Q42H) alteration is located in exon 2 (coding exon 2) of the DHRS7B gene. This alteration results from a G to C substitution at nucleotide position 126, causing the glutamine (Q) at amino acid position 42 to be replaced by a histidine (H). 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	0.18
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.18	.;T;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.069	D
MetaRNN	Uncertain	0.66	D;D;D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Uncertain	2.1	.;M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.6	.;D;.
REVEL	Uncertain	0.64
Sift	Benign	0.037	.;D;.
Sift4G	Benign	0.088	T;T;T
Polyphen		1.0	.;D;.
Vest4		0.57, 0.58
MutPred		0.51		Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);.;
MVP		0.77
MPC		0.65
ClinPred		0.90	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.13
gMVP		0.48

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: chr17-21075436;