chr12-53938989-T-TCGG

Variant names:

• chr12-53938989-T-TCGG
• rs34115456
• NM_017410.3:c.96_98dupCGG

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS2

The NM_017410.3(HOXC13):​c.96_98dupCGG​(p.Gly33dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000339 in 1,505,410 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: HOXC13 NM_017410.3 disruptive_inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.0760
• Publications: 0 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 -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_017410.3
• BP6: Variant 12-53938989-T-TCGG is Benign according to our data. Variant chr12-53938989-T-TCGG is described in ClinVar as Likely_benign. ClinVar VariationId is 2071049.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR,AD gene

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.96_98dupCGG	p.Gly33dup	disruptive_inframe_insertion	Exon 1 of 2	NP_059106.2
	HOXC13-AS	NR_047507.1		n.173+479_173+481dupCCG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXC13	ENST00000243056.5	TSL:1 MANE Select	c.96_98dupCGG	p.Gly33dup	disruptive_inframe_insertion	Exon 1 of 2	ENSP00000243056.3	P31276
	HOXC13-AS	ENST00000512916.3	TSL:3	n.222+479_222+481dupCCG		intron	N/A
	HOXC13-AS	ENST00000810609.1		n.181+479_181+481dupCCG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00192 AC: 292 AN: 152040 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00669

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

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: 0.0000441

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000152 AC: 16 AN: 105460 AF XY: 0.000150

Gnomad AFR exome AF: 0.00293

Gnomad AMR exome AF: 0.000262

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000231

Gnomad OTH exome AF: 0.000329

GnomAD4 exome AF: 0.000163 AC: 220 AN: 1353260 Hom.: 0 Cov.: 32 AF XY: 0.000138 AC XY: 92 AN XY: 668024

African (AFR) AF: 0.00608 AC: 170 AN: 27938

American (AMR) AF: 0.000404 AC: 13 AN: 32164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23812

East Asian (EAS) AF: 0.00 AC: 0 AN: 31738

South Asian (SAS) AF: 0.0000131 AC: 1 AN: 76418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5174

European-Non Finnish (NFE) AF: 0.0000113 AC: 12 AN: 1065240

Other (OTH) AF: 0.000427 AC: 24 AN: 56198

GnomAD4 genome AF: 0.00191 AC: 290 AN: 152150 Hom.: 2 Cov.: 32 AF XY: 0.00187 AC XY: 139 AN XY: 74386

African (AFR) AF: 0.00663 AC: 275 AN: 41508

American (AMR) AF: 0.000523 AC: 8 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67974

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00227

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	HOXC13-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.076
Mutation Taster		=76/24	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs34115456; hg19: chr12-54332773;