chr22-17138587-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDHD5	NM_033070.3	c.898G>A	p.Gly300Ser	missense_variant	Exon 7 of 8	ENST00000336737.8	NP_149061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDHD5	ENST00000336737.8	c.898G>A	p.Gly300Ser	missense_variant	Exon 7 of 8	1	NM_033070.3	ENSP00000337358.4

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.898G>A (p.G300S) alteration is located in exon 7 (coding exon 7) of the CECR5 gene. This alteration results from a G to A substitution at nucleotide position 898, causing the glycine (G) at amino acid position 300 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-0.96	T
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Benign	0.16
Sift	Benign	0.047	D;D
Sift4G	Uncertain	0.038	D;D
Polyphen		0.72	P;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-17619477;