chr17-8121559-A-G

Variant names:

• chr17-8121559-A-G
• rs535914789
• NM_001165967.2:c.*12T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001165967.2(HES7):​c.*12T>C variant causes a 3 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HES7 NM_001165967.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

Genes affected

HES7 (HGNC:15977): (hes family bHLH transcription factor 7) This gene encodes a member of the hairy and enhancer of split family of bHLH transcription factors. The mouse ortholog of this gene is regulated by Notch signaling. The protein functions as a transcriptional repressor, and is implicated in correct patterning of the axial skeleton. A mutation in this gene has been shown to result in spondylocostal dysostosis. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HES7	NM_001165967.2	c.*12T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000541682.7	NP_001159439.1
HES7	NM_032580.4	c.*12T>C		3_prime_UTR_variant	Exon 4 of 4		NP_115969.2
HES7	XM_047436940.1	c.*12T>C		3_prime_UTR_variant	Exon 3 of 3		XP_047292896.1
HES7	XM_047436941.1	c.*12T>C		3_prime_UTR_variant	Exon 5 of 5		XP_047292897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HES7	ENST00000541682	c.*12T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_001165967.2	ENSP00000446205.2
HES7	ENST00000317814.8	c.*12T>C		downstream_gene_variant		1		ENSP00000314774.4
HES7	ENST00000577735.1	c.*245T>C		downstream_gene_variant		3		ENSP00000462491.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.8
DANN	Benign	0.24

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs535914789; hg19: chr17-8024877;