Genetic Variant NM_006497.4:c.503C>A (chr17-2057193-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006497.4(HIC1):c.503C>A(p.Ala168Asp) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

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: 3.45

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1032514).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006497.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIC1	NM_006497.4	MANE Select	c.503C>A	p.Ala168Asp	missense	Exon 2 of 2	NP_006488.2	Q14526-2
	HIC1	NM_001098202.1		c.560C>A	p.Ala187Asp	missense	Exon 2 of 2	NP_001091672.1	Q14526-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HIC1	ENST00000619757.5	TSL:1 MANE Select	c.503C>A	p.Ala168Asp	missense	Exon 2 of 2	ENSP00000477858.1	Q14526-2
HIC1	ENST00000399849.4	TSL:1	c.503C>A	p.Ala168Asp	missense	Exon 2 of 2	ENSP00000382742.2	Q14526-2
HIC1	ENST00000322941.3	TSL:5	c.560C>A	p.Ala187Asp	missense	Exon 2 of 2	ENSP00000314080.3	Q14526-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1231738

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

605520

African (AFR)

AF:

0.00

AC:

AN:

24194

American (AMR)

AF:

0.00

AC:

AN:

15560

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18658

East Asian (EAS)

AF:

0.00

AC:

AN:

25956

South Asian (SAS)

AF:

0.00

AC:

AN:

60128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30242

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3510

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1003560

Other (OTH)

AF:

0.00

AC:

AN:

49930

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.28

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.37

LIST_S2

Uncertain

0.87

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PhyloP100

3.5

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-2.0

REVEL

Benign

0.027

Sift

Benign

0.065

Sift4G

Benign

0.27

Polyphen

0.0030

Vest4

0.12

MutPred

0.20

Gain of relative solvent accessibility (P = 0.0082)

MVP

0.13

ClinPred

0.55

GERP RS

1.1

Varity_R

0.34

gMVP

0.62

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over