chr22-17138677-C-G

Variant names:

• chr22-17138677-C-G
• NM_033070.3:c.808G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_033070.3(HDHD5):​c.808G>C​(p.Glu270Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 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: 3.67
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26439667).

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.808G>C	p.Glu270Gln	missense	Exon 7 of 8	NP_149061.1	Q9BXW7-1
	HDHD5	NM_017829.6		c.718G>C	p.Glu240Gln	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.808G>C	p.Glu270Gln	missense	Exon 7 of 8	ENSP00000337358.4	Q9BXW7-1
	HDHD5	ENST00000155674.9	TSL:1	c.718G>C	p.Glu240Gln	missense	Exon 7 of 8	ENSP00000155674.5	Q9BXW7-2
	HDHD5	ENST00000477157.5	TSL:1	n.2651G>C		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

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	0.094
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.073
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.92	T
PhyloP100		3.7
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.14
Sift	Benign	0.037	D
Sift4G	Uncertain	0.045	D
Polyphen		0.61	P
Vest4		0.24
MutPred		0.26		Loss of ubiquitination at K269 (P = 0.0285)
MVP		0.16
MPC		0.28
ClinPred		0.94	D
GERP RS		3.7
Varity_R		0.15
gMVP		0.67
Mutation Taster		=59/41	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

hg19: chr22-17619567;