chr17-2057202-C-A

Variant names:

• chr17-2057202-C-A
• NM_006497.4:c.512C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006497.4(HIC1):​c.512C>A​(p.Pro171Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000809 in 1,236,722 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: HIC1 NM_006497.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.607

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

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=0.108768106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIC1	NM_006497.4	c.512C>A	p.Pro171Gln	missense_variant	Exon 2 of 2	ENST00000619757.5	NP_006488.2
HIC1	NM_001098202.1	c.569C>A	p.Pro190Gln	missense_variant	Exon 2 of 2		NP_001091672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIC1	ENST00000619757.5	c.512C>A	p.Pro171Gln	missense_variant	Exon 2 of 2	1	NM_006497.4	ENSP00000477858.1
HIC1	ENST00000399849.4	c.512C>A	p.Pro171Gln	missense_variant	Exon 2 of 2	1		ENSP00000382742.2
HIC1	ENST00000322941.3	c.569C>A	p.Pro190Gln	missense_variant	Exon 2 of 2	5		ENSP00000314080.3
HIC1	ENST00000571990.1	c.*223C>A		downstream_gene_variant		1		ENSP00000460268.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.09e-7 AC: 1 AN: 1236722 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 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: 9.94e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.19	.;.;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.57	T;.;T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	.;.;N
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.62	N;.;N
REVEL	Benign	0.035
Sift	Benign	0.11	T;.;T
Sift4G	Benign	0.21	T;T;T
Polyphen		0.0010	.;.;B
Vest4		0.18
MutPred		0.18		.;.;Gain of solvent accessibility (P = 0.0109);
MVP		0.22
ClinPred		0.11	T
GERP RS		2.5
Varity_R		0.071
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-1960496;