chr14-73478803-A-T

Variant names:

• chr14-73478803-A-T
• NM_001220484.1:c.2884T>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001220484.1(HEATR4):​c.2884T>A​(p.Ser962Thr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: HEATR4 NM_001220484.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.439

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061088473).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEATR4	NM_001220484.1	c.2884T>A	p.Ser962Thr	missense_variant	Exon 18 of 18	ENST00000553558.6	NP_001207413.1
HEATR4	NM_203309.2	c.2884T>A	p.Ser962Thr	missense_variant	Exon 17 of 17		NP_976054.2
HEATR4	XM_047431370.1	c.2884T>A	p.Ser962Thr	missense_variant	Exon 17 of 17		XP_047287326.1
HEATR4	XM_047431371.1	c.1615T>A	p.Ser539Thr	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.2884T>A	p.Ser962Thr	missense_variant	Exon 18 of 18	2	NM_001220484.1	ENSP00000450444.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2884T>A (p.S962T) alteration is located in exon 18 (coding exon 16) of the HEATR4 gene. This alteration results from a T to A substitution at nucleotide position 2884, causing the serine (S) at amino acid position 962 to be replaced by a threonine (T). 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	0.074
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.88
DEOGEN2	Benign	0.0020	T;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.23	.;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.061	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.17	N;N
REVEL	Benign	0.029
Sift	Benign	0.35	T;T
Sift4G	Benign	0.11	T;T
Polyphen		0.12	B;B
Vest4		0.18
MutPred		0.20		Loss of glycosylation at S962 (P = 0.0335);Loss of glycosylation at S962 (P = 0.0335);
MVP		0.30
MPC		0.10
ClinPred		0.056	T
GERP RS		2.5
Varity_R		0.046
gMVP		0.038

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: chr14-73945508;