rs758711363

Variant names:

• chr17-2057306-C-T
• rs758711363
• NM_006497.4:c.616C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_006497.4(HIC1):​c.616C>T​(p.Pro206Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,498,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: HIC1 NM_006497.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.102
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.029298156).
• BS2: High AC in GnomAd4 at 13 AD gene.

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.616C>T	p.Pro206Ser	missense	Exon 2 of 2	NP_006488.2	Q14526-2
	HIC1	NM_001098202.1		c.673C>T	p.Pro225Ser	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.616C>T	p.Pro206Ser	missense	Exon 2 of 2	ENSP00000477858.1	Q14526-2
	HIC1	ENST00000399849.4	TSL:1	c.616C>T	p.Pro206Ser	missense	Exon 2 of 2	ENSP00000382742.2	Q14526-2
	HIC1	ENST00000322941.3	TSL:5	c.673C>T	p.Pro225Ser	missense	Exon 2 of 2	ENSP00000314080.3	Q14526-1

Frequencies

GnomAD3 genomes AF: 0.0000857 AC: 13 AN: 151688 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD2 exomes AF: 0.0000172 AC: 2 AN: 116132 AF XY: 0.0000150

Gnomad AFR exome AF: 0.000273

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000199

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000223 AC: 3 AN: 1346768 Hom.: 0 Cov.: 32 AF XY: 0.00000300 AC XY: 2 AN XY: 666954

African (AFR) AF: 0.0000359 AC: 1 AN: 27848

American (AMR) AF: 0.00 AC: 0 AN: 31144

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23244

East Asian (EAS) AF: 0.00 AC: 0 AN: 30122

South Asian (SAS) AF: 0.00 AC: 0 AN: 76076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33912

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4242

European-Non Finnish (NFE) AF: 9.39e-7 AC: 1 AN: 1064744

Other (OTH) AF: 0.0000180 AC: 1 AN: 55436

GnomAD4 genome AF: 0.0000857 AC: 13 AN: 151688 Hom.: 0 Cov.: 34 AF XY: 0.000108 AC XY: 8 AN XY: 74080

African (AFR) AF: 0.000314 AC: 13 AN: 41382

American (AMR) AF: 0.00 AC: 0 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67858

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000110

ExAC AF: 0.00000948 AC: 1

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	Benign	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.61	T
M_CAP	Pathogenic	0.40	D
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.10
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	0.020	N
REVEL	Benign	0.026
Sift	Benign	0.72	T
Sift4G	Benign	0.90	T
Polyphen		0.012	B
Vest4		0.18
MutPred		0.19		Gain of phosphorylation at P225 (P = 0.0378)
MVP		0.19
ClinPred		0.020	T
GERP RS		1.8
Varity_R		0.056
gMVP		0.19
Mutation Taster		=94/6	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

dbSNP: rs758711363; hg19: chr17-1960600;