14-73478628-C-A

Variant names:

• chr14-73478628-C-A
• NM_001220484.1:c.3059G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001220484.1(HEATR4):​c.3059G>T​(p.Gly1020Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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: 31)
• Consequence: HEATR4 NM_001220484.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.331

Genes affected

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

ENSG00000251393 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.097632945).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEATR4	NM_001220484.1	c.3059G>T	p.Gly1020Val	missense_variant	Exon 18 of 18	ENST00000553558.6	NP_001207413.1
HEATR4	NM_203309.2	c.3059G>T	p.Gly1020Val	missense_variant	Exon 17 of 17		NP_976054.2
HEATR4	XM_047431370.1	c.3059G>T	p.Gly1020Val	missense_variant	Exon 17 of 17		XP_047287326.1
HEATR4	XM_047431371.1	c.1790G>T	p.Gly597Val	missense_variant	Exon 15 of 15		XP_047287327.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEATR4	ENST00000553558.6	c.3059G>T	p.Gly1020Val	missense_variant	Exon 18 of 18	2	NM_001220484.1	ENSP00000450444.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3059G>T (p.G1020V) alteration is located in exon 18 (coding exon 16) of the HEATR4 gene. This alteration results from a G to T substitution at nucleotide position 3059, causing the glycine (G) at amino acid position 1020 to be replaced by a valine (V). 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	0.088
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	3.3
DANN	Benign	0.88
DEOGEN2	Benign	0.0012	T;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.33	.;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.098	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.11	N;N
REVEL	Benign	0.075
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.91	P;P
Vest4		0.14
MutPred		0.10		Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);
MVP		0.055
MPC		0.14
ClinPred		0.21	T
GERP RS		1.6
Varity_R		0.062
gMVP		0.014

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: chr14-73945333;