NM_033070.3:c.898G>A

Variant names:

• chr22-17138587-C-T
• rs769003367
• NM_033070.3:c.898G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_033070.3(HDHD5):​c.898G>A​(p.Gly300Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HDHD5 NM_033070.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.44
• Publications: 0 publications found

Genes affected

HDHD5 (HGNC:1843): (haloacid dehalogenase like hydrolase domain containing 5) Predicted to be involved in glycerophospholipid biosynthetic process. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033070.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDHD5	NM_033070.3	MANE Select	c.898G>A	p.Gly300Ser	missense	Exon 7 of 8	NP_149061.1	Q9BXW7-1
	HDHD5	NM_017829.6		c.808G>A	p.Gly270Ser	missense	Exon 7 of 8	NP_060299.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDHD5	ENST00000336737.8	TSL:1 MANE Select	c.898G>A	p.Gly300Ser	missense	Exon 7 of 8	ENSP00000337358.4	Q9BXW7-1
	HDHD5	ENST00000155674.9	TSL:1	c.808G>A	p.Gly270Ser	missense	Exon 7 of 8	ENSP00000155674.5	Q9BXW7-2
	HDHD5	ENST00000477157.5	TSL:1	n.2741G>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461846 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.091	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.96	T
PhyloP100		5.4
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.16
Sift	Benign	0.047	D
Sift4G	Uncertain	0.038	D
Polyphen		0.72	P
Vest4		0.62
MutPred		0.40		Gain of phosphorylation at G300 (P = 0.0267)
MVP		0.35
MPC		0.57
ClinPred		0.96	D
GERP RS		4.4
Varity_R		0.48
gMVP		0.75
Mutation Taster		=26/74	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs769003367; hg19: chr22-17619477;