14-73478611-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001220484.1(HEATR4):​c.3076C>T​(p.Leu1026Phe) 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 Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Consequence

HEATR4
NM_001220484.1 missense

Scores

1
18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.901
Variant links:
Genes affected
HEATR4 (HGNC:16761): (HEAT repeat containing 4) Predicted to enable oxidoreductase activity. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.026982397).
BP6
Variant 14-73478611-G-A is Benign according to our data. Variant chr14-73478611-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2490072.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HEATR4NM_001220484.1 linkuse as main transcriptc.3076C>T p.Leu1026Phe missense_variant 18/18 ENST00000553558.6 NP_001207413.1 Q86WZ0
HEATR4NM_203309.2 linkuse as main transcriptc.3076C>T p.Leu1026Phe missense_variant 17/17 NP_976054.2 Q86WZ0
HEATR4XM_047431370.1 linkuse as main transcriptc.3076C>T p.Leu1026Phe missense_variant 17/17 XP_047287326.1
HEATR4XM_047431371.1 linkuse as main transcriptc.1807C>T p.Leu603Phe missense_variant 15/15 XP_047287327.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HEATR4ENST00000553558.6 linkuse as main transcriptc.3076C>T p.Leu1026Phe missense_variant 18/182 NM_001220484.1 ENSP00000450444.2 Q86WZ0

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsFeb 27, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.071
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
0.24
DANN
Benign
0.45
DEOGEN2
Benign
0.00070
T;T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.069
N
LIST_S2
Benign
0.25
.;T
M_CAP
Benign
0.0025
T
MetaRNN
Benign
0.027
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N;N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
0.17
N;N
REVEL
Benign
0.0020
Sift
Benign
0.74
T;T
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.0020
B;B
Vest4
0.17
MutPred
0.19
Gain of methylation at K1021 (P = 0.0979);Gain of methylation at K1021 (P = 0.0979);
MVP
0.014
MPC
0.12
ClinPred
0.056
T
GERP RS
-2.6
Varity_R
0.046
gMVP
0.011

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: chr14-73945316; COSMIC: COSV105238817; COSMIC: COSV105238817; API