rs201946311

Variant names:

• chr9-113373843-C-G
• NM_001304509.2:c.512G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-113373843-C-G
• chr9-113373843-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001304509.2(HDHD3):​c.512G>C​(p.Arg171Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R171H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HDHD3 NM_001304509.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82

Genes affected

HDHD3 (HGNC:28171): (haloacid dehalogenase like hydrolase domain containing 3) Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.793

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDHD3	NM_001304509.2	c.512G>C	p.Arg171Pro	missense_variant	Exon 3 of 3	ENST00000374180.4	NP_001291438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDHD3	ENST00000374180.4	c.512G>C	p.Arg171Pro	missense_variant	Exon 3 of 3	1	NM_001304509.2	ENSP00000363295.3
HDHD3	ENST00000238379.9	c.512G>C	p.Arg171Pro	missense_variant	Exon 2 of 2	1		ENSP00000238379.5
HDHD3	ENST00000485934.1	n.*45G>C		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461780 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 727186

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.50	D
LIST_S2	Uncertain	0.89	.;D
M_CAP	Benign	0.0093	T
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.9	M;M
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.15
Sift	Benign	0.074	T;T
Sift4G	Benign	0.25	T;T
Polyphen		1.0	D;D
Vest4		0.70
MutPred		0.63		Gain of catalytic residue at P170 (P = 0.012);Gain of catalytic residue at P170 (P = 0.012);
MVP		0.55
MPC		0.68
ClinPred		0.98	D
GERP RS		3.6
Varity_R		0.96
gMVP		0.82

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: chr9-116136123;