chr17-2057159-C-T

Variant names:

• chr17-2057159-C-T
• NM_006497.4:c.469C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006497.4(HIC1):​c.469C>T​(p.Arg157Trp) 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0350
• Publications: 0 publications found

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]

ACMG classification

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=0.122427285).

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.469C>T	p.Arg157Trp	missense	Exon 2 of 2	NP_006488.2	Q14526-2
	HIC1	NM_001098202.1		c.526C>T	p.Arg176Trp	missense	Exon 2 of 2	NP_001091672.1	Q14526-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIC1	ENST00000619757.5	TSL:1 MANE Select	c.469C>T	p.Arg157Trp	missense	Exon 2 of 2	ENSP00000477858.1	Q14526-2
	HIC1	ENST00000399849.4	TSL:1	c.469C>T	p.Arg157Trp	missense	Exon 2 of 2	ENSP00000382742.2	Q14526-2
	HIC1	ENST00000322941.3	TSL:5	c.526C>T	p.Arg176Trp	missense	Exon 2 of 2	ENSP00000314080.3	Q14526-1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1169474 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 569168

African (AFR) AF: 0.00 AC: 0 AN: 23044

American (AMR) AF: 0.00 AC: 0 AN: 9336

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15384

East Asian (EAS) AF: 0.00 AC: 0 AN: 25696

South Asian (SAS) AF: 0.00 AC: 0 AN: 43898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26842

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3186

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 974860

Other (OTH) AF: 0.00 AC: 0 AN: 47228

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.69	D
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.23	N
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.035
PrimateAI	Pathogenic	0.95	D
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.026
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.010	D
Polyphen		0.078	B
Vest4		0.16
MutPred		0.36		Loss of methylation at R176 (P = 0.0068)
MVP		0.16
ClinPred		0.60	D
GERP RS		0.57
Varity_R		0.16
gMVP		0.48
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

hg19: chr17-1960453;