3-124970777-G-A

Variant summary

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

The NM_020733.2(HEG1):​c.4021C>T​(p.Leu1341Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,946 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

HEG1
NM_020733.2 missense

Scores

5
11
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.33
Variant links:
Genes affected
HEG1 (HGNC:29227): (heart development protein with EGF like domains 1) Predicted to enable calcium ion binding activity. Involved in several processes, including negative regulation of Rho protein signal transduction; negative regulation of Rho-dependent protein serine/threonine kinase activity; and negative regulation of membrane permeability. Located in cell-cell junction. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HEG1NM_020733.2 linkuse as main transcriptc.4021C>T p.Leu1341Phe missense_variant 17/17 ENST00000311127.9 NP_065784.1 Q9ULI3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HEG1ENST00000311127.9 linkuse as main transcriptc.4021C>T p.Leu1341Phe missense_variant 17/175 NM_020733.2 ENSP00000311502.3 Q9ULI3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000827
AC:
2
AN:
241890
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
130898
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000296
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000168
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1457946
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
724688
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000452
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
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 09, 2024The c.4021C>T (p.L1341F) alteration is located in exon 17 (coding exon 17) of the HEG1 gene. This alteration results from a C to T substitution at nucleotide position 4021, causing the leucine (L) at amino acid position 1341 to be replaced by a phenylalanine (F). 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
Pathogenic
0.82
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
0.050
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.29
T;.
Eigen
Pathogenic
0.74
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Uncertain
0.16
D
MetaRNN
Uncertain
0.67
D;D
MetaSVM
Uncertain
0.77
D
MutationAssessor
Benign
0.69
N;.
PrimateAI
Uncertain
0.70
T
PROVEAN
Uncertain
-2.5
D;D
REVEL
Uncertain
0.48
Sift
Uncertain
0.0040
D;D
Sift4G
Uncertain
0.013
D;D
Polyphen
1.0
D;.
Vest4
0.55
MutPred
0.28
Loss of sheet (P = 0.0181);.;
MVP
0.96
MPC
0.53
ClinPred
0.86
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.21
gMVP
0.69

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1192078620; hg19: chr3-124689621; API