chr9-113374123-C-T

Variant names:

• chr9-113374123-C-T
• rs763106655
• NM_001304509.2:c.232G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001304509.2(HDHD3):​c.232G>A​(p.Val78Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,448,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. V78L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: HDHD3 NM_001304509.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37998068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDHD3	NM_001304509.2	c.232G>A	p.Val78Met	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.232G>A	p.Val78Met	missense_variant	Exon 3 of 3	1	NM_001304509.2	ENSP00000363295.3
HDHD3	ENST00000238379.9	c.232G>A	p.Val78Met	missense_variant	Exon 2 of 2	1		ENSP00000238379.5
HDHD3	ENST00000485934.1	n.678G>A		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000404 AC: 1 AN: 247786 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134016

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000103

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1448222 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 717434

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000388

Gnomad4 EAS exome AF: 0.00

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.: 33

Alfa AF: 0.0000254 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	T;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.85	.;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.38	T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Pathogenic	2.9	M;M
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.84	N;N
REVEL	Benign	0.23
Sift	Uncertain	0.012	D;D
Sift4G	Uncertain	0.027	D;D
Polyphen		1.0	D;D
Vest4		0.47
MutPred		0.46		Gain of catalytic residue at V78 (P = 0.045);Gain of catalytic residue at V78 (P = 0.045);
MVP		0.47
MPC		0.56
ClinPred		0.91	D
GERP RS		4.8
Varity_R		0.25
gMVP		0.74

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

LitVar

Other links and lift over

dbSNP: rs763106655; hg19: chr9-116136403;