22-17138724-G-C

Variant names:

• chr22-17138724-G-C
• rs750756548
• NM_033070.3:c.761C>G

Variant summary

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

The NM_033070.3(HDHD5):​c.761C>G​(p.Thr254Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. T254I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HDHD5 NM_033070.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.99
• 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.761C>G	p.Thr254Ser	missense	Exon 7 of 8	NP_149061.1	Q9BXW7-1
	HDHD5	NM_017829.6		c.671C>G	p.Thr224Ser	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.761C>G	p.Thr254Ser	missense	Exon 7 of 8	ENSP00000337358.4	Q9BXW7-1
	HDHD5	ENST00000155674.9	TSL:1	c.671C>G	p.Thr224Ser	missense	Exon 7 of 8	ENSP00000155674.5	Q9BXW7-2
	HDHD5	ENST00000477157.5	TSL:1	n.2604C>G		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.043	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-1.0	T
PhyloP100		6.0
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.11
Sift	Uncertain	0.021	D
Sift4G	Benign	0.16	T
Polyphen		0.20	B
Vest4		0.52
MutPred		0.62		Loss of helix (P = 0.0795)
MVP		0.31
MPC		0.21
ClinPred		0.92	D
GERP RS		4.7
Varity_R		0.24
gMVP		0.63
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs750756548; hg19: chr22-17619614;