rs201910585

Variant names:

• chr3-124977881-C-A
• rs201910585
• NM_020733.2:c.3799G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-124977881-C-A
• chr3-124977881-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020733.2(HEG1):​c.3799G>T​(p.Ala1267Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000703 in 1,423,208 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A1267T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: HEG1 NM_020733.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.54
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020733.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEG1	NM_020733.2	MANE Select	c.3799G>T	p.Ala1267Ser	missense	Exon 15 of 17	NP_065784.1	Q9ULI3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEG1	ENST00000311127.9	TSL:5 MANE Select	c.3799G>T	p.Ala1267Ser	missense	Exon 15 of 17	ENSP00000311502.3	Q9ULI3-1
	HEG1	ENST00000650592.2		c.4099G>T	p.Ala1367Ser	missense	Exon 16 of 18	ENSP00000515478.1	A0A994J6K3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1423208 Hom.: 0 Cov.: 29 AF XY: 0.00000142 AC XY: 1 AN XY: 704282

African (AFR) AF: 0.00 AC: 0 AN: 32556

American (AMR) AF: 0.00 AC: 0 AN: 39304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25390

East Asian (EAS) AF: 0.00 AC: 0 AN: 37682

South Asian (SAS) AF: 0.0000124 AC: 1 AN: 80580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5664

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092196

Other (OTH) AF: 0.00 AC: 0 AN: 59014

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Uncertain	0.21	D
MutationAssessor	Benign	0.81	L
PhyloP100		4.5
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.50
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.017	D
Polyphen		0.39	B
Vest4		0.61
MutPred		0.59		Loss of sheet (P = 0.0104)
MVP		0.87
MPC		0.38
ClinPred		0.66	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.062
gMVP		0.71
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs201910585; hg19: chr3-124696725;