NM_152888.3:c.734-3436G>A

Variant names:

• chr8-138836586-C-T
• rs9650564
• NM_152888.3:c.734-3436G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152888.3(COL22A1):​c.734-3436G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 151,966 control chromosomes in the GnomAD database, including 22,317 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (22317 hom., cov: 32)
• Consequence: COL22A1 NM_152888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL22A1	NM_152888.3	MANE Select	c.734-3436G>A		intron	N/A	NP_690848.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL22A1	ENST00000303045.11	TSL:1 MANE Select	c.734-3436G>A		intron	N/A	ENSP00000303153.6

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80853 AN: 151848 Hom.: 22309 Cov.: 32

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.551

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.532 AC: 80882 AN: 151966 Hom.: 22317 Cov.: 32 AF XY: 0.536 AC XY: 39786 AN XY: 74270

African (AFR) AF: 0.380 AC: 15739 AN: 41422

American (AMR) AF: 0.604 AC: 9235 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2119 AN: 3470

East Asian (EAS) AF: 0.659 AC: 3382 AN: 5130

South Asian (SAS) AF: 0.549 AC: 2645 AN: 4820

European-Finnish (FIN) AF: 0.613 AC: 6469 AN: 10546

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39383 AN: 67970

Other (OTH) AF: 0.550 AC: 1161 AN: 2110

Alfa AF: 0.540 Hom.: 7480

Bravo AF: 0.522

Asia WGS AF: 0.554 AC: 1929 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.43
DANN	Benign	0.30
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs9650564; hg19: chr8-139848829;