rs780220370

Variant names:

• chr14-73478737-G-A
• NM_001220484.1:c.2950C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-73478737-G-A
• chr14-73478737-G-C

Variant summary

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

The NM_001220484.1(HEATR4):​c.2950C>T​(p.Pro984Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P984A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HEATR4 NM_001220484.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437

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=0.03946668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEATR4	NM_001220484.1	c.2950C>T	p.Pro984Ser	missense_variant	Exon 18 of 18	ENST00000553558.6	NP_001207413.1
HEATR4	NM_203309.2	c.2950C>T	p.Pro984Ser	missense_variant	Exon 17 of 17		NP_976054.2
HEATR4	XM_047431370.1	c.2950C>T	p.Pro984Ser	missense_variant	Exon 17 of 17		XP_047287326.1
HEATR4	XM_047431371.1	c.1681C>T	p.Pro561Ser	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.2950C>T	p.Pro984Ser	missense_variant	Exon 18 of 18	2	NM_001220484.1	ENSP00000450444.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.77
DEOGEN2	Benign	0.00093	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.24	.;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.039	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.36	N;N
REVEL	Benign	0.011
Sift	Benign	0.20	T;T
Sift4G	Benign	0.18	T;T
Polyphen		0.0	B;B
Vest4		0.23
MutPred		0.20		Gain of phosphorylation at P984 (P = 0.006);Gain of phosphorylation at P984 (P = 0.006);
MVP		0.014
MPC		0.11
ClinPred		0.030	T
GERP RS		-1.2
Varity_R		0.026
gMVP		0.043

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: chr14-73945442; COSMIC: COSV105238818; COSMIC: COSV105238818;