8-79765663-G-A

Variant names:

• chr8-79765663-G-A
• NM_012258.4:c.440C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012258.4(HEY1):​c.440C>T​(p.Ser147Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HEY1 NM_012258.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.37
• Publications: 0 publications found

Genes affected

HEY1 (HGNC:4880): (hes related family bHLH transcription factor with YRPW motif 1) This gene encodes a nuclear protein belonging to the hairy and enhancer of split-related (HESR) family of basic helix-loop-helix (bHLH)-type transcriptional repressors. Expression of this gene is induced by the Notch and c-Jun signal transduction pathways. Two similar and redundant genes in mouse are required for embryonic cardiovascular development, and are also implicated in neurogenesis and somitogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

LINC01607 (HGNC:51660): (long intergenic non-protein coding RNA 1607)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3715604).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012258.4. 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
	HEY1	NM_012258.4	MANE Select	c.440C>T	p.Ser147Phe	missense	Exon 5 of 5	NP_036390.3
	HEY1	NM_001040708.2		c.452C>T	p.Ser151Phe	missense	Exon 5 of 5	NP_001035798.1	Q9Y5J3-2
	HEY1	NM_001282851.2		c.170C>T	p.Ser57Phe	missense	Exon 2 of 2	NP_001269780.1	B4DEI9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEY1	ENST00000354724.8	TSL:1 MANE Select	c.440C>T	p.Ser147Phe	missense	Exon 5 of 5	ENSP00000346761.3	Q9Y5J3-1
	HEY1	ENST00000337919.9	TSL:1	c.452C>T	p.Ser151Phe	missense	Exon 5 of 5	ENSP00000338272.5	Q9Y5J3-2
	HEY1	ENST00000435063.4	TSL:1	n.251C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.4	L
PhyloP100		6.4
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.19
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.013	D
Polyphen		0.77	P
Vest4		0.25
MutPred		0.34		Loss of disorder (P = 0.0449)
MVP		0.21
MPC		1.3
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.78
gMVP		0.48
Mutation Taster		=54/46	polymorphism

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

Other links and lift over

hg19: chr8-80677898;