12-53938949-C-CTTA

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PM4_Supporting BP6_Moderate BA1

The NM_017410.3(HOXC13):c.45_47dup(p.Leu15_Met16insIle) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.0208 in 1,558,642 control chromosomes in the GnomAD database, including 614 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (42 hom., cov: 32)
  • Exomes 𝑓: 0.021 (572 hom.)
• Consequence: HOXC13 NM_017410.3 inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.86

Genes affected

HOXC13 (HGNC:5125): (homeobox C13) This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, which are located on different chromosomes and consist of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXC genes located in a cluster on chromosome 12. The product of this gene may play a role in the development of hair, nail, and filiform papilla. [provided by RefSeq, Jul 2008]

HOXC13-AS (HGNC:43753): (HOXC13 antisense RNA)

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_017410.3. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 12-53938949-C-CTTA is Benign according to our data. Variant chr12-53938949-C-CTTA is described in ClinVar as [Benign]. Clinvar id is 2033340.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.068 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOXC13	NM_017410.3	c.45_47dup	p.Leu15_Met16insIle	inframe_insertion	1/2	ENST00000243056.5
HOXC13-AS	NR_047507.1	n.173+521_173+522insTAA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOXC13	ENST00000243056.5	c.45_47dup	p.Leu15_Met16insIle	inframe_insertion	1/2	1	NM_017410.3	P1
HOXC13-AS	ENST00000512916.2	n.173+521_173+522insTAA		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0157 AC: 2387 AN: 152210 Hom.: 42 Cov.: 32

Gnomad AFR AF: 0.00311

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0740

Gnomad FIN AF: 0.0138

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0209

Gnomad OTH AF: 0.0205

GnomAD3 exomes AF: 0.0219 AC: 3780 AN: 172822 Hom.: 108 AF XY: 0.0259 AC XY: 2488 AN XY: 95896

Gnomad AFR exome AF: 0.00402

Gnomad AMR exome AF: 0.00722

Gnomad ASJ exome AF: 0.0166

Gnomad EAS exome AF: 0.000238

Gnomad SAS exome AF: 0.0736

Gnomad FIN exome AF: 0.0106

Gnomad NFE exome AF: 0.0176

Gnomad OTH exome AF: 0.0247

GnomAD4 exome AF: 0.0214 AC: 30039 AN: 1406320 Hom.: 572 Cov.: 32 AF XY: 0.0231 AC XY: 16106 AN XY: 697224

Gnomad4 AFR exome AF: 0.00312

Gnomad4 AMR exome AF: 0.00858

Gnomad4 ASJ exome AF: 0.0163

Gnomad4 EAS exome AF: 0.0000554

Gnomad4 SAS exome AF: 0.0764

Gnomad4 FIN exome AF: 0.0129

Gnomad4 NFE exome AF: 0.0191

Gnomad4 OTH exome AF: 0.0220

GnomAD4 genome AF: 0.0157 AC: 2388 AN: 152322 Hom.: 42 Cov.: 32 AF XY: 0.0163 AC XY: 1214 AN XY: 74474

Gnomad4 AFR AF: 0.00310

Gnomad4 AMR AF: 0.0124

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0743

Gnomad4 FIN AF: 0.0138

Gnomad4 NFE AF: 0.0209

Gnomad4 OTH AF: 0.0203

Alfa AF: 0.0182 Hom.: 23

Bravo AF: 0.0132

Asia WGS AF: 0.0220 AC: 75 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34421542; hg19: chr12-54332733;