Variant 17-2057154-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006497.4(HIC1):c.464C>T(p.Pro155Leu) variant causes a missense 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HIC1
NM_006497.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.691

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]

HIC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 (MetaRNN=0.061178356).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIC1	NM_006497.4 link	c.464C>T	p.Pro155Leu	missense_variant	2/2	ENST00000619757.5	NP_006488.2	Q14526-2A0PJI1
HIC1	NM_001098202.1 link	c.521C>T	p.Pro174Leu	missense_variant	2/2		NP_001091672.1	Q14526-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HIC1	ENST00000619757.5 link	c.464C>T	p.Pro155Leu	missense_variant	2/2	1	NM_006497.4	ENSP00000477858.1	Q14526-2
HIC1	ENST00000399849.4 link	c.464C>T	p.Pro155Leu	missense_variant	2/2	1		ENSP00000382742.2	Q14526-2
HIC1	ENST00000322941.3 link	c.521C>T	p.Pro174Leu	missense_variant	2/2	5		ENSP00000314080.3	Q14526-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1158494

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

562286

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:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2024

The c.521C>T (p.P174L) alteration is located in exon 2 (coding exon 2) of the HIC1 gene. This alteration results from a C to T substitution at nucleotide position 521, causing the proline (P) at amino acid position 174 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.20

.;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.65

T;.;T

M_CAP

Benign

0.067

MetaRNN

Benign

0.061

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

.;.;N

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.4

N;.;N

REVEL

Benign

0.040

Sift

Benign

0.44

T;.;T

Sift4G

Benign

0.42

T;T;T

Polyphen

0.0010

.;.;B

Vest4

0.10

MutPred

0.24

.;.;Loss of relative solvent accessibility (P = 0.0186);

MVP

0.14

ClinPred

0.089

GERP RS

2.6

Varity_R

0.057

gMVP

0.27

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over