8-119067400-CCA-C

Variant names:

• chr8-119067400-CCA-C
• rs749987061
• NM_006438.5:c.128_129delCA

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_006438.5(COLEC10):​c.128_129delCA​(p.Thr43AsnfsTer9) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,752 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: COLEC10 NM_006438.5 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 3.06
• Publications: 1 publications found

Genes affected

COLEC10 (HGNC:2220): (collectin subfamily member 10) This gene encodes a member of the C-lectin family, proteins that possess collagen-like sequences and carbohydrate recognition domains. The other members of this family are secreted proteins and bind to carbohydrate antigens on microorganisms facilitating their recognition and removal. This gene product is a cytosolic protein, a characteristic that suggests that it may have different biological functions than other C-lectins. [provided by RefSeq, Jul 2008]

COLEC10 Gene-Disease associations (from GenCC):

• 3MC syndrome 3

  Inheritance: AR Classification: STRONG Submitted by: G2P
• 3MC syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000254278 (HGNC:):

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 8-119067400-CCA-C is Pathogenic according to our data. Variant chr8-119067400-CCA-C is described in ClinVar as [Pathogenic]. Clinvar id is 992663.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COLEC10	NM_006438.5	c.128_129delCA	p.Thr43AsnfsTer9	frameshift_variant	Exon 1 of 6	ENST00000332843.3	NP_006429.2
COLEC10	NM_001324095.2	c.-59-22271_-59-22270delCA		intron_variant	Intron 3 of 7		NP_001311024.1
LOC101927513	NR_134297.1	n.1109+272_1109+273delTG		intron_variant	Intron 1 of 1
COLEC10	XM_005250756.4	c.-59-22271_-59-22270delCA		intron_variant	Intron 1 of 5		XP_005250813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COLEC10	ENST00000332843.3	c.128_129delCA	p.Thr43AsnfsTer9	frameshift_variant	Exon 1 of 6	1	NM_006438.5	ENSP00000332723.2
ENSG00000254278	ENST00000518362.2	n.1109+272_1109+273delTG		intron_variant	Intron 1 of 1	1
COLEC10	ENST00000521788.1	n.236-22271_236-22270delCA		intron_variant	Intron 2 of 6	3

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152066 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000797 AC: 2 AN: 250956 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461686 Hom.: 0 AF XY: 0.00000413 AC XY: 3 AN XY: 727136

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39692

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111864

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152066 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74292

African (AFR) AF: 0.00 AC: 0 AN: 41388

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

3MC syndrome 3 Pathogenic:1

Jan 01, 2020

Medical Genetics Laboratory, Tarbiat Modares University

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1
Mutation Taster		=15/185	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs749987061; hg19: chr8-120079639;