Variant 8-138826669-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_152888.3(COL22A1):c.958A>G(p.Ser320Gly) variant causes a missense change. The variant allele was found at a frequency of 0.809 in 1,612,904 control chromosomes in the GnomAD database, including 528,102 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.82 ( 51177 hom., cov: 29)

Exomes 𝑓: 0.81 ( 476925 hom. )

Consequence

COL22A1
NM_152888.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.05

Variant links:

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]

COL22A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.695768E-7).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL22A1	NM_152888.3 linkuse as main transcript	c.958A>G	p.Ser320Gly	missense_variant	6/65	ENST00000303045.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL22A1	ENST00000303045.11 linkuse as main transcript	c.958A>G	p.Ser320Gly	missense_variant	6/65	1	NM_152888.3	P1	Q8NFW1-1
COL22A1	ENST00000517515.1 linkuse as main transcript	n.358A>G		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

AF:

0.820

AC:

124519

AN:

151838

Hom.:

51116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.861

Gnomad AMI

AF:

0.789

Gnomad AMR

AF:

0.825

Gnomad ASJ

AF:

0.778

Gnomad EAS

AF:

0.743

Gnomad SAS

AF:

0.870

Gnomad FIN

AF:

0.791

Gnomad MID

AF:

0.835

Gnomad NFE

AF:

0.804

Gnomad OTH

AF:

0.801

GnomAD3 exomes

AF:

0.814

AC:

204483

AN:

251314

Hom.:

83410

AF XY:

0.815

AC XY:

110689

AN XY:

135822

show subpopulations

Gnomad AFR exome

AF:

0.863

Gnomad AMR exome

AF:

0.833

Gnomad ASJ exome

AF:

0.782

Gnomad EAS exome

AF:

0.736

Gnomad SAS exome

AF:

0.871

Gnomad FIN exome

AF:

0.792

Gnomad NFE exome

AF:

0.805

Gnomad OTH exome

AF:

0.811

GnomAD4 exome

AF:

0.808

AC:

1179769

AN:

1460948

Hom.:

476925

Cov.:

AF XY:

0.809

AC XY:

587997

AN XY:

726804

show subpopulations

Gnomad4 AFR exome

AF:

0.864

Gnomad4 AMR exome

AF:

0.830

Gnomad4 ASJ exome

AF:

0.780

Gnomad4 EAS exome

AF:

0.757

Gnomad4 SAS exome

AF:

0.871

Gnomad4 FIN exome

AF:

0.791

Gnomad4 NFE exome

AF:

0.803

Gnomad4 OTH exome

AF:

0.805

GnomAD4 genome

AF:

0.820

AC:

124633

AN:

151956

Hom.:

51177

Cov.:

AF XY:

0.820

AC XY:

60905

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.862

Gnomad4 AMR

AF:

0.825

Gnomad4 ASJ

AF:

0.778

Gnomad4 EAS

AF:

0.743

Gnomad4 SAS

AF:

0.869

Gnomad4 FIN

AF:

0.791

Gnomad4 NFE

AF:

0.804

Gnomad4 OTH

AF:

0.804

Alfa

AF:

0.808

Hom.:

124391

Bravo

AF:

0.822

TwinsUK

AF:

0.811

AC:

3008

ALSPAC

AF:

0.800

AC:

3084

ESP6500AA

AF:

0.866

AC:

3816

ESP6500EA

AF:

0.810

AC:

6970

ExAC

AF:

0.814

AC:

98884

Asia WGS

AF:

0.807

AC:

2808

AN:

3478

EpiCase

AF:

0.804

EpiControl

AF:

0.810

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.042

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.45

DEOGEN2

Benign

0.00040

T;.

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.36

T;T

MetaRNN

Benign

5.7e-7

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-2.9

N;N

MutationTaster

Benign

0.97

P;P

PrimateAI

Uncertain

0.63

PROVEAN

Benign

2.5

N;N

REVEL

Benign

0.097

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.12

MPC

0.077

ClinPred

0.015

GERP RS

5.2

Varity_R

0.059

gMVP

0.29

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over