Variant chr8-138594184-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000303045.11(COL22A1):c.4448T>A(p.Leu1483His) variant causes a missense change. The variant allele was found at a frequency of 0.00616 in 1,572,466 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0060 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0062 ( 52 hom. )

Consequence

COL22A1
ENST00000303045.11 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.07

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008943975).

BP6

Variant 8-138594184-A-T is Benign according to our data. Variant chr8-138594184-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2658850.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL22A1	NM_152888.3 linkuse as main transcript	c.4448T>A	p.Leu1483His	missense_variant	63/65	ENST00000303045.11	NP_690848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL22A1	ENST00000303045.11 linkuse as main transcript	c.4448T>A	p.Leu1483His	missense_variant	63/65	1	NM_152888.3	ENSP00000303153	P1	Q8NFW1-1
COL22A1	ENST00000341807.8 linkuse as main transcript	n.2133T>A		non_coding_transcript_exon_variant	37/39	1

Frequencies

GnomAD3 genomes

AF:

0.00599

AC:

911

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00556

Gnomad ASJ

AF:

0.0452

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0168

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00630

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00669

AC:

1395

AN:

208650

Hom.:

AF XY:

0.00653

AC XY:

747

AN XY:

114376

show subpopulations

Gnomad AFR exome

AF:

0.00131

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.0453

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000394

Gnomad FIN exome

AF:

0.0156

Gnomad NFE exome

AF:

0.00592

Gnomad OTH exome

AF:

0.00809

GnomAD4 exome

AF:

0.00617

AC:

8769

AN:

1420150

Hom.:

Cov.:

AF XY:

0.00618

AC XY:

4365

AN XY:

706504

show subpopulations

Gnomad4 AFR exome

AF:

0.000910

Gnomad4 AMR exome

AF:

0.00195

Gnomad4 ASJ exome

AF:

0.0438

Gnomad4 EAS exome

AF:

0.0000277

Gnomad4 SAS exome

AF:

0.000707

Gnomad4 FIN exome

AF:

0.0164

Gnomad4 NFE exome

AF:

0.00567

Gnomad4 OTH exome

AF:

0.00737

GnomAD4 genome

AF:

0.00598

AC:

911

AN:

152316

Hom.:

Cov.:

AF XY:

0.00639

AC XY:

476

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.00555

Gnomad4 ASJ

AF:

0.0452

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0168

Gnomad4 NFE

AF:

0.00631

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00946

Hom.:

Bravo

AF:

0.00516

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00872

AC:

ExAC

AF:

0.00575

AC:

698

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

COL22A1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.0070

T;.

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.55

T;T

MetaRNN

Benign

0.0089

T;T

MetaSVM

Uncertain

0.40

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.8

N;.

REVEL

Uncertain

0.57

Sift

Uncertain

0.027

D;.

Sift4G

Uncertain

0.034

D;D

Polyphen

1.0

D;.

Vest4

0.45

MVP

0.50

MPC

0.11

ClinPred

0.030

GERP RS

5.9

Varity_R

0.26

gMVP

0.47

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over