17-8121703-C-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001165967.2(HES7):​c.561G>C​(p.Pro187=) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Consequence

HES7
NM_001165967.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.186
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 17-8121703-C-G is Benign according to our data. Variant chr17-8121703-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1945841.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.186 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HES7NM_001165967.2 linkuse as main transcriptc.561G>C p.Pro187= synonymous_variant 4/4 ENST00000541682.7
HES7NM_032580.4 linkuse as main transcriptc.546G>C p.Pro182= synonymous_variant 4/4
HES7XM_047436940.1 linkuse as main transcriptc.657G>C p.Pro219= synonymous_variant 3/3
HES7XM_047436941.1 linkuse as main transcriptc.648G>C p.Pro216= synonymous_variant 5/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HES7ENST00000541682.7 linkuse as main transcriptc.561G>C p.Pro187= synonymous_variant 4/41 NM_001165967.2 A1Q9BYE0-2
HES7ENST00000317814.8 linkuse as main transcriptc.546G>C p.Pro182= synonymous_variant 4/41 P4Q9BYE0-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpOct 04, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
6.9
DANN
Benign
0.79

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: chr17-8025021; API