rs759366814

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006497.4(HIC1):​c.256C>A​(p.Arg86Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,082 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R86C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

HIC1
NM_006497.4 missense

Scores

3
11
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.10
Variant links:
Genes affected
HIC1 (HGNC:4909): (HIC ZBTB transcriptional repressor 1) This gene functions as a growth regulatory and tumor repressor gene. Hypermethylation or deletion of the region of this gene have been associated with tumors and the contiguous-gene syndrome, Miller-Dieker syndrome. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HIC1NM_006497.4 linkc.256C>A p.Arg86Ser missense_variant Exon 2 of 2 ENST00000619757.5 NP_006488.2 Q14526-2A0PJI1
HIC1NM_001098202.1 linkc.313C>A p.Arg105Ser missense_variant Exon 2 of 2 NP_001091672.1 Q14526-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HIC1ENST00000619757.5 linkc.256C>A p.Arg86Ser missense_variant Exon 2 of 2 1 NM_006497.4 ENSP00000477858.1 Q14526-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1455082
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
723716
show subpopulations
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.78
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.050
CADD
Pathogenic
30
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.44
T;.;.;D
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.85
T;D;.;D
M_CAP
Pathogenic
0.57
D
MetaRNN
Uncertain
0.63
D;D;D;D
MetaSVM
Benign
-0.39
T
MutationAssessor
Benign
0.93
.;.;.;L
PrimateAI
Pathogenic
0.92
D
PROVEAN
Uncertain
-3.5
.;D;.;D
REVEL
Uncertain
0.42
Sift
Uncertain
0.0030
.;D;.;D
Sift4G
Benign
0.20
T;D;D;D
Polyphen
1.0
.;.;.;D
Vest4
0.69, 0.69, 0.69
MutPred
0.48
.;.;.;Gain of glycosylation at R105 (P = 0.0806);
MVP
0.64
ClinPred
0.96
D
GERP RS
4.3
Varity_R
0.58
gMVP
0.87

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: chr17-1960240; API