chr12-53938949-C-CTTA

Variant names:

• chr12-53938949-C-CTTA
• rs34421542
• NM_017410.3:c.45_47dupTAT

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 1P and 10B. PM4_Supporting BP6_Moderate BA1

The NM_017410.3(HOXC13):​c.45_47dupTAT​(p.Leu15_Met16insIle) variant causes a disruptive 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 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.86
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017410.3. 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
	HOXC13	NM_017410.3	MANE Select	c.45_47dupTAT	p.Leu15_Met16insIle	disruptive_inframe_insertion	Exon 1 of 2	NP_059106.2
	HOXC13-AS	NR_047507.1		n.173+519_173+521dupTAA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXC13	ENST00000243056.5	TSL:1 MANE Select	c.45_47dupTAT	p.Leu15_Met16insIle	disruptive_inframe_insertion	Exon 1 of 2	ENSP00000243056.3	P31276
	HOXC13-AS	ENST00000512916.3	TSL:3	n.222+519_222+521dupTAA		intron	N/A
	HOXC13-AS	ENST00000810609.1		n.181+519_181+521dupTAA		intron	N/A

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

GnomAD2 exomes AF: 0.0219 AC: 3780 AN: 172822 AF XY: 0.0259

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 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

African (AFR) AF: 0.00312 AC: 96 AN: 30790

American (AMR) AF: 0.00858 AC: 352 AN: 41022

Ashkenazi Jewish (ASJ) AF: 0.0163 AC: 409 AN: 25018

East Asian (EAS) AF: 0.0000554 AC: 2 AN: 36114

South Asian (SAS) AF: 0.0764 AC: 6240 AN: 81724

European-Finnish (FIN) AF: 0.0129 AC: 469 AN: 36448

Middle Eastern (MID) AF: 0.0631 AC: 352 AN: 5576

European-Non Finnish (NFE) AF: 0.0191 AC: 20829 AN: 1090976

Other (OTH) AF: 0.0220 AC: 1290 AN: 58652

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

African (AFR) AF: 0.00310 AC: 129 AN: 41584

American (AMR) AF: 0.0124 AC: 190 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5176

South Asian (SAS) AF: 0.0743 AC: 359 AN: 4832

European-Finnish (FIN) AF: 0.0138 AC: 147 AN: 10620

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0209 AC: 1423 AN: 68010

Other (OTH) AF: 0.0203 AC: 43 AN: 2116

Alfa AF: 0.0182 Hom.: 23

Bravo AF: 0.0132

Asia WGS AF: 0.0220 AC: 75 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.9
Mutation Taster		=55/45	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs34421542; hg19: chr12-54332733; COSMIC: COSV54499960;