Genetic Variant HIC1:p.Pro171Leu (chr17-2057202-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_006497.4(HIC1):c.512C>T(p.Pro171Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 151,530 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: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HIC1
NM_006497.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.607

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=0.13784409).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIC1	NM_006497.4 link	c.512C>T	p.Pro171Leu	missense_variant	Exon 2 of 2	ENST00000619757.5	NP_006488.2	Q14526-2A0PJI1
HIC1	NM_001098202.1 link	c.569C>T	p.Pro190Leu	missense_variant	Exon 2 of 2		NP_001091672.1	Q14526-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HIC1	ENST00000619757.5 link	c.512C>T	p.Pro171Leu	missense_variant	Exon 2 of 2	1	NM_006497.4	ENSP00000477858.1	Q14526-2
HIC1	ENST00000399849.4 link	c.512C>T	p.Pro171Leu	missense_variant	Exon 2 of 2	1		ENSP00000382742.2	Q14526-2
HIC1	ENST00000322941.3 link	c.569C>T	p.Pro190Leu	missense_variant	Exon 2 of 2	5		ENSP00000314080.3	Q14526-1
HIC1	ENST00000571990.1 link	c.*223C>T		downstream_gene_variant		1		ENSP00000460268.1	I3L388

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151530

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1236720

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

608262

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

AF:

0.00000660

AC:

AN:

151530

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74020

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000658

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

.;.;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.41

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.69

T;.;T

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;.;N

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-1.5

N;.;N

REVEL

Benign

0.016

Sift

Uncertain

0.0080

D;.;T

Sift4G

Benign

0.061

T;T;D

Polyphen

0.029

.;.;B

Vest4

0.13

MutPred

0.21

.;.;Loss of glycosylation at P190 (P = 0.0406);

MVP

0.26

ClinPred

0.24

GERP RS

2.5

Varity_R

0.060

gMVP

0.41

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over