17-8121673-G-C

Variant names:

• chr17-8121673-G-C
• NM_001165967.2:c.591C>G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001165967.2(HES7):​c.591C>G​(p.Pro197Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000766 in 1,175,186 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000077 (0 hom.)
• Consequence: HES7 NM_001165967.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.781

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=0.781 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HES7	NM_001165967.2	c.591C>G	p.Pro197Pro	synonymous_variant	Exon 4 of 4	ENST00000541682.7	NP_001159439.1
HES7	NM_032580.4	c.576C>G	p.Pro192Pro	synonymous_variant	Exon 4 of 4		NP_115969.2
HES7	XM_047436940.1	c.687C>G	p.Pro229Pro	synonymous_variant	Exon 3 of 3		XP_047292896.1
HES7	XM_047436941.1	c.678C>G	p.Pro226Pro	synonymous_variant	Exon 5 of 5		XP_047292897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HES7	ENST00000541682.7	c.591C>G	p.Pro197Pro	synonymous_variant	Exon 4 of 4	1	NM_001165967.2	ENSP00000446205.2
HES7	ENST00000317814.8	c.576C>G	p.Pro192Pro	synonymous_variant	Exon 4 of 4	1		ENSP00000314774.4
HES7	ENST00000577735.1	c.*131C>G		downstream_gene_variant		3		ENSP00000462491.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000766 AC: 9 AN: 1175186 Hom.: 0 Cov.: 30 AF XY: 0.00000531 AC XY: 3 AN XY: 564666

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000231

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000716

Gnomad4 OTH exome AF: 0.0000207

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	11
DANN	Benign	0.88

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-8024991;