chr14-60149363-T-C

Position:

• chr14-60149363-T-C

Variant summary

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

The NM_016029.4(DHRS7):​c.962A>G​(p.Lys321Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: DHRS7 NM_016029.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.44

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=0.19726601).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHRS7	NM_016029.4	c.962A>G	p.Lys321Arg	missense_variant	6/7	ENST00000557185.6
DHRS7	NM_001322280.2	c.812A>G	p.Lys271Arg	missense_variant	6/7
DHRS7	NM_001322282.2	c.722A>G	p.Lys241Arg	missense_variant	5/6
DHRS7	NM_001322281.2	c.542A>G	p.Lys181Arg	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHRS7	ENST00000557185.6	c.962A>G	p.Lys321Arg	missense_variant	6/7	1	NM_016029.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461820 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727210

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	0.0044	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.0074	T;T;.
Eigen	Benign	0.037
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.3	L;L;.
MutationTaster	Benign	0.71	N;N;N;D
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.66	N;N;N
REVEL	Benign	0.27
Sift	Benign	0.23	T;T;T
Sift4G	Benign	0.34	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.14
MutPred		0.36		Loss of ubiquitination at K321 (P = 0.0174);Loss of ubiquitination at K321 (P = 0.0174);.;
MVP		0.96
MPC		0.039
ClinPred		0.47	T
GERP RS		3.2
Varity_R		0.056
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr14-60616081;