chr6-116120066-T-TGGG

Variant names:

• chr6-116120066-T-TGGG
• rs140722
• NM_000493.4:c.*6_*7insCCC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000493.4(COL10A1):​c.*6_*7insCCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.882 in 1,608,076 control chromosomes in the GnomAD database, including 627,330 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.91 (63188 hom., cov: 0)
  • Exomes 𝑓: 0.88 (564142 hom.)
• Consequence: COL10A1 NM_000493.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 2.01
• Publications: 2 publications found

Genes affected

COL10A1 (HGNC:2185): (collagen type X alpha 1 chain) This gene encodes the alpha chain of type X collagen, a short chain collagen expressed by hypertrophic chondrocytes during endochondral ossification. Unlike type VIII collagen, the other short chain collagen, type X collagen is a homotrimer. Mutations in this gene are associated with Schmid type metaphyseal chondrodysplasia (SMCD) and Japanese type spondylometaphyseal dysplasia (SMD). [provided by RefSeq, Jul 2008]

NT5DC1 (HGNC:21556): (5'-nucleotidase domain containing 1) While the exact function of the protein encoded by this gene is not known, it belongs to the 5'(3')-deoxyribonucleotidase family. [provided by RefSeq, May 2010]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 6-116120066-T-TGGG is Benign according to our data. Variant chr6-116120066-T-TGGG is described in ClinVar as Benign. ClinVar VariationId is 256259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000493.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL10A1	NM_000493.4	MANE Select	c.*6_*7insCCC		3_prime_UTR	Exon 3 of 3	NP_000484.2
	NT5DC1	NM_152729.3	MANE Select	c.529+2122_529+2123insGGG		intron	N/A	NP_689942.2
	COL10A1	NM_001424106.1		c.*6_*7insCCC		3_prime_UTR	Exon 3 of 3	NP_001411035.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL10A1	ENST00000651968.1	MANE Select	c.*6_*7insCCC		3_prime_UTR	Exon 3 of 3	ENSP00000498802.1
	COL10A1	ENST00000243222.8	TSL:1	c.*6_*7insCCC		3_prime_UTR	Exon 3 of 3	ENSP00000243222.4
	COL10A1	ENST00000327673.4	TSL:1	c.*6_*7insCCC		3_prime_UTR	Exon 2 of 2	ENSP00000327368.4

Frequencies

GnomAD3 genomes AF: 0.910 AC: 138163 AN: 151890 Hom.: 63126 Cov.: 0

Gnomad AFR AF: 0.976

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.927

Gnomad ASJ AF: 0.913

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.975

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.926

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.895

GnomAD2 exomes AF: 0.910 AC: 228062 AN: 250524 AF XY: 0.911

Gnomad AFR exome AF: 0.979

Gnomad AMR exome AF: 0.944

Gnomad ASJ exome AF: 0.917

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.877

Gnomad NFE exome AF: 0.865

Gnomad OTH exome AF: 0.898

GnomAD4 exome AF: 0.879 AC: 1280140 AN: 1456068 Hom.: 564142 Cov.: 33 AF XY: 0.882 AC XY: 639181 AN XY: 724788

African (AFR) AF: 0.980 AC: 32706 AN: 33364

American (AMR) AF: 0.942 AC: 42106 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 23905 AN: 26102

East Asian (EAS) AF: 1.00 AC: 39664 AN: 39674

South Asian (SAS) AF: 0.972 AC: 83740 AN: 86144

European-Finnish (FIN) AF: 0.870 AC: 46427 AN: 53374

Middle Eastern (MID) AF: 0.939 AC: 5389 AN: 5738

European-Non Finnish (NFE) AF: 0.861 AC: 952436 AN: 1106776

Other (OTH) AF: 0.893 AC: 53767 AN: 60180

GnomAD4 genome AF: 0.910 AC: 138283 AN: 152008 Hom.: 63188 Cov.: 0 AF XY: 0.912 AC XY: 67769 AN XY: 74314

African (AFR) AF: 0.976 AC: 40511 AN: 41498

American (AMR) AF: 0.927 AC: 14173 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.913 AC: 3166 AN: 3466

East Asian (EAS) AF: 0.999 AC: 5149 AN: 5152

South Asian (SAS) AF: 0.975 AC: 4706 AN: 4826

European-Finnish (FIN) AF: 0.869 AC: 9177 AN: 10560

Middle Eastern (MID) AF: 0.931 AC: 270 AN: 290

European-Non Finnish (NFE) AF: 0.862 AC: 58549 AN: 67914

Other (OTH) AF: 0.896 AC: 1890 AN: 2110

Alfa AF: 0.874 Hom.: 30778

Asia WGS AF: 0.984 AC: 3421 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Metaphyseal chondrodysplasia (1)
-	-	1	Metaphyseal chondrodysplasia, Schmid type (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs140722; hg19: chr6-116441229; COSMIC: COSV54571852; COSMIC: COSV54571852;