Variant 10-70741107-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_080722.4(ADAMTS14):c.1869C>G(p.Ser623Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 1,613,710 control chromosomes in the GnomAD database, including 303,385 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 0.63 ( 30522 hom., cov: 33)

Exomes 𝑓: 0.61 ( 272863 hom. )

Consequence

ADAMTS14
NM_080722.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.524

Variant links:

Genes affected

ADAMTS14 (HGNC:14899): (ADAM metallopeptidase with thrombospondin type 1 motif 14) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme cleaves amino-terminal propeptides from type I procollagen, a necessary step in the formation of collagen fibers. Mutations in this gene may be associated with osteoarthritis in human patients. [provided by RefSeq, May 2016]

ADAMTS14 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP7

Synonymous conserved (PhyloP=0.524 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS14	NM_080722.4 link	c.1869C>G	p.Ser623Ser	synonymous_variant	12/22	ENST00000373207.2	NP_542453.2	Q8WXS8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS14	ENST00000373207.2 link	c.1869C>G	p.Ser623Ser	synonymous_variant	12/22	1	NM_080722.4	ENSP00000362303.1		Q8WXS8-1
ADAMTS14	ENST00000373208.5 link	c.1878C>G	p.Ser626Ser	synonymous_variant	12/22	2		ENSP00000362304.1		Q8WXS8-4

Frequencies

GnomAD3 genomes

AF:

0.631

AC:

95919

AN:

152020

Hom.:

30501

Cov.:

show subpopulations

Gnomad AFR

AF:

0.662

Gnomad AMI

AF:

0.368

Gnomad AMR

AF:

0.579

Gnomad ASJ

AF:

0.677

Gnomad EAS

AF:

0.870

Gnomad SAS

AF:

0.627

Gnomad FIN

AF:

0.690

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.598

Gnomad OTH

AF:

0.611

GnomAD3 exomes

AF:

0.628

AC:

157775

AN:

251038

Hom.:

50348

AF XY:

0.628

AC XY:

85259

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.658

Gnomad AMR exome

AF:

0.552

Gnomad ASJ exome

AF:

0.677

Gnomad EAS exome

AF:

0.867

Gnomad SAS exome

AF:

0.616

Gnomad FIN exome

AF:

0.685

Gnomad NFE exome

AF:

0.598

Gnomad OTH exome

AF:

0.618

GnomAD4 exome

AF:

0.609

AC:

889763

AN:

1461572

Hom.:

272863

Cov.:

AF XY:

0.610

AC XY:

443283

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.663

Gnomad4 AMR exome

AF:

0.555

Gnomad4 ASJ exome

AF:

0.676

Gnomad4 EAS exome

AF:

0.863

Gnomad4 SAS exome

AF:

0.618

Gnomad4 FIN exome

AF:

0.682

Gnomad4 NFE exome

AF:

0.593

Gnomad4 OTH exome

AF:

0.624

GnomAD4 genome

AF:

0.631

AC:

95991

AN:

152138

Hom.:

30522

Cov.:

AF XY:

0.636

AC XY:

47300

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.662

Gnomad4 AMR

AF:

0.578

Gnomad4 ASJ

AF:

0.677

Gnomad4 EAS

AF:

0.870

Gnomad4 SAS

AF:

0.627

Gnomad4 FIN

AF:

0.690

Gnomad4 NFE

AF:

0.598

Gnomad4 OTH

AF:

0.613

Alfa

AF:

0.565

Hom.:

3164

Bravo

AF:

0.621

Asia WGS

AF:

0.719

AC:

2495

AN:

3478

EpiCase

AF:

0.600

EpiControl

AF:

0.595

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

8.7

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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