NM_152888.3:c.958A>T

Variant names:

• chr8-138826669-T-A
• rs2292927
• NM_152888.3:c.958A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152888.3(COL22A1):​c.958A>T​(p.Ser320Cys) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COL22A1 NM_152888.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.05
• Publications: 34 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17416999).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152888.3. 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
	COL22A1	NM_152888.3	MANE Select	c.958A>T	p.Ser320Cys	missense	Exon 6 of 65	NP_690848.1	Q8NFW1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL22A1	ENST00000303045.11	TSL:1 MANE Select	c.958A>T	p.Ser320Cys	missense	Exon 6 of 65	ENSP00000303153.6	Q8NFW1-1
	COL22A1	ENST00000903590.1		c.958A>T	p.Ser320Cys	missense	Exon 6 of 64	ENSP00000573649.1
	COL22A1	ENST00000903591.1		c.958A>T	p.Ser320Cys	missense	Exon 6 of 62	ENSP00000573650.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151880 Hom.: 0 Cov.: 29

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1461612 Hom.: 0 Cov.: 41 AF XY: 0.00 AC XY: 0 AN XY: 727128

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111792

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151880 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 74168

African (AFR) AF: 0.00 AC: 0 AN: 41338

American (AMR) AF: 0.00 AC: 0 AN: 15244

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 224737

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.020
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		6.1
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.12
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.37	B
Vest4		0.30
MutPred		0.53		Loss of phosphorylation at Y319 (P = 0.1011)
MVP		0.14
MPC		0.082
ClinPred		0.87	D
GERP RS		5.2
Varity_R		0.14
gMVP		0.45
Mutation Taster		=89/11	polymorphism

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: rs2292927; hg19: chr8-139838912;