chr8-138606391-C-G

Variant names:

• chr8-138606391-C-G
• rs749493332
• NM_152888.3:c.4094G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152888.3(COL22A1):​c.4094G>C​(p.Arg1365Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: COL22A1 NM_152888.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.95

Genes affected

COL22A1 (HGNC:22989): (collagen type XXII alpha 1 chain) This gene encodes member of the collagen family which is thought to contribute to the stabilization of myotendinous junctions and strengthen skeletal muscle attachments during contractile activity. It belongs to the fibril-associated collagens with interrupted triple helix (FACIT) subset of the collagen superfamily, which associate with collagen fibers through their C-terminal collagenous domains and mediate protein-protein interactions through their N-terminal noncollagenous domains. The encoded protein is deposited in the basement membrane zone of the myotendinous junction which is present only at the tissue junctions of muscles, tendons, the heart, articular cartilage, and skin. A knockdown of the orthologous zebrafish gene induces a muscular dystrophy by disruption of the myotendinous junction. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL22A1	NM_152888.3	c.4094G>C	p.Arg1365Pro	missense_variant	Exon 58 of 65	ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11	c.4094G>C	p.Arg1365Pro	missense_variant	Exon 58 of 65	1	NM_152888.3	ENSP00000303153.6
COL22A1	ENST00000341807.8	n.1779G>C		non_coding_transcript_exon_variant	Exon 32 of 39	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0020	T;.
Eigen	Benign	-0.021
Eigen_PC	Benign	0.14
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.70	T;D
M_CAP	Benign	0.070	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Uncertain	0.14	D
MutationAssessor	Benign	-0.66	N;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.92	N;.
REVEL	Uncertain	0.42
Sift	Benign	0.27	T;.
Sift4G	Benign	0.67	T;T
Polyphen		1.0	D;.
Vest4		0.51
MutPred		0.46		Gain of glycosylation at R1365 (P = 0.0118);.;
MVP		0.42
MPC		0.12
ClinPred		0.82	D
GERP RS		5.4
Varity_R		0.34
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs749493332; hg19: chr8-139618634;