Variant chr17-2057489-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006497.4(HIC1):c.799C>G(p.Leu267Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000751 in 1,332,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

HIC1
NM_006497.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.07

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18347621).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIC1	NM_006497.4 linkuse as main transcript	c.799C>G	p.Leu267Val	missense_variant	2/2	ENST00000619757.5	NP_006488.2
HIC1	NM_001098202.1 linkuse as main transcript	c.856C>G	p.Leu286Val	missense_variant	2/2		NP_001091672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIC1	ENST00000619757.5 linkuse as main transcript	c.799C>G	p.Leu267Val	missense_variant	2/2	1	NM_006497.4	ENSP00000477858	P4	Q14526-2
HIC1	ENST00000399849.4 linkuse as main transcript	c.799C>G	p.Leu267Val	missense_variant	2/2	1		ENSP00000382742	P4	Q14526-2
HIC1	ENST00000322941.3 linkuse as main transcript	c.856C>G	p.Leu286Val	missense_variant	2/2	5		ENSP00000314080	A1	Q14526-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.51e-7

AC:

AN:

1332294

Hom.:

Cov.:

AF XY:

0.00000152

AC XY:

AN XY:

656800

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000333

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.:

Bravo

AF:

0.00000756

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

Dec 26, 2023

The c.856C>G (p.L286V) alteration is located in exon 2 (coding exon 2) of the HIC1 gene. This alteration results from a C to G substitution at nucleotide position 856, causing the leucine (L) at amino acid position 286 to be replaced by a valine (V). 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

0.14

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.3

DANN

Benign

0.94

DEOGEN2

Benign

0.15

.;.;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.54

T;.;T

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

.;.;N

MutationTaster

Benign

0.99

N;N

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.39

N;.;N

REVEL

Benign

0.026

Sift

Benign

0.14

T;.;T

Sift4G

Benign

0.22

T;T;T

Polyphen

0.46

.;.;P

Vest4

0.17

MutPred

0.20

.;.;Loss of glycosylation at P287 (P = 0.1103);

MVP

0.18

ClinPred

0.030

GERP RS

1.9

Varity_R

0.036

gMVP

0.080

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over