rs769983717

Variant names:

• chr14-73498168-C-G
• NM_001220484.1:c.2533G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-73498168-C-G
• chr14-73498168-C-T

Variant summary

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

The NM_001220484.1(HEATR4):​c.2533G>C​(p.Asp845His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: HEATR4 NM_001220484.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.53

Genes affected

HEATR4 (HGNC:16761): (HEAT repeat containing 4) Predicted to enable oxidoreductase activity. [provided by Alliance of Genome Resources, Apr 2022]

ACOT1 (HGNC:33128): (acyl-CoA thioesterase 1) Enables acyl-CoA hydrolase activity. Involved in acyl-CoA metabolic process; long-chain fatty acid metabolic process; and very long-chain fatty acid metabolic process. Located in cytosol. [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=0.3588028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEATR4	NM_001220484.1	c.2533G>C	p.Asp845His	missense_variant	Exon 14 of 18	ENST00000553558.6	NP_001207413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEATR4	ENST00000553558.6	c.2533G>C	p.Asp845His	missense_variant	Exon 14 of 18	2	NM_001220484.1	ENSP00000450444.2
HEATR4	ENST00000334988.2	c.2533G>C	p.Asp845His	missense_variant	Exon 13 of 17	1		ENSP00000335447.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459580 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725702

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T;T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.76	.;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.4	N;N
REVEL	Benign	0.071
Sift	Uncertain	0.015	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.99	D;D
Vest4		0.40
MutPred		0.34		Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);
MVP		0.37
MPC		0.52
ClinPred		0.82	D
GERP RS		4.2
Varity_R		0.13
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-73964872;