HES4 p.Glu120Glu

Variant names:

• chr1-999364-C-C
• NM_021170.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr1-999365--
• chr1-999365-C-T

Variant summary

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

The NM_021170.4(HES4):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: HES4 NM_021170.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.804
• Publications: 0 publications found

Genes affected

HES4 (HGNC:24149): (hes family bHLH transcription factor 4) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in anterior/posterior pattern specification and regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [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_021170.4. 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
	HES4	NM_021170.4	MANE Select	c.		exon_region	Exon 4 of 4	NP_066993.1	Q9HCC6
	HES4	NM_001142467.2		c.		exon_region	Exon 3 of 3	NP_001135939.1	E9PB28
	HES4	NM_001410700.1		c.		exon_region	Exon 3 of 3	NP_001397629.1	D6REB3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HES4	ENST00000304952.11	TSL:1 MANE Select	c.		exon_region	Exon 4 of 4	ENSP00000304595.7	Q9HCC6
	HES4	ENST00000428771.6	TSL:2	c.		exon_region	Exon 3 of 3	ENSP00000393198.2	E9PB28
	HES4	ENST00000854802.1		c.		exon_region	Exon 4 of 4	ENSP00000524863.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.80

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-934744;