17-2056799-G-A

Variant names:

• chr17-2056799-G-A
• NM_006497.4:c.109G>A

Variant summary

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

The NM_006497.4(HIC1):​c.109G>A​(p.Ala37Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,416 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HIC1 NM_006497.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.54

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIC1	NM_006497.4	c.109G>A	p.Ala37Thr	missense_variant	Exon 2 of 2	ENST00000619757.5	NP_006488.2
HIC1	NM_001098202.1	c.166G>A	p.Ala56Thr	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.109G>A	p.Ala37Thr	missense_variant	Exon 2 of 2	1	NM_006497.4	ENSP00000477858.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460416 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726484

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: 8.99e-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	Uncertain	0.53
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	.;T;.;.;.;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D;T;T;.;T;T
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.60	D;D;D;D;D;D
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	0.49	.;.;.;.;.;N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.3	.;.;N;.;.;N
REVEL	Uncertain	0.37
Sift	Benign	0.060	.;.;T;.;.;T
Sift4G	Benign	0.53	T;T;T;T;T;T
Polyphen		1.0	.;.;.;.;.;D
Vest4		0.38, 0.33, 0.38
MutPred		0.42		.;.;.;.;.;Gain of helix (P = 0.132);
MVP		0.58
ClinPred		0.96	D
GERP RS		4.1
Varity_R		0.19
gMVP		0.56

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: chr17-1960093; COSMIC: COSV99558390; COSMIC: COSV99558390;