Variant 5-65151950-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_197941.4(ADAMTS6):c.3245-5G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 1,607,320 control chromosomes in the GnomAD database, including 204,239 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.42 ( 15123 hom., cov: 32)

Exomes 𝑓: 0.51 ( 189116 hom. )

Consequence

ADAMTS6
NM_197941.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002000

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.622

Variant links:

Genes affected

ADAMTS6 (HGNC:222): (ADAM metallopeptidase with thrombospondin type 1 motif 6) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) 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. Expression of this gene may be regulated by the cytokine TNF-alpha. [provided by RefSeq, Mar 2016]

ADAMTS6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS6	NM_197941.4 linkuse as main transcript	c.3245-5G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000381055.8	NP_922932.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
ADAMTS6	ENST00000381055.8 linkuse as main transcript	c.3245-5G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_197941.4	ENSP00000370443	P1	Q9UKP5-1
ADAMTS6	ENST00000381052.8 linkuse as main transcript	c.*2517-5G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant	2		ENSP00000424377		Q9UKP5-4
ADAMTS6	ENST00000314351.9 linkuse as main transcript	n.905-5G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64565

AN:

151842

Hom.:

15122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.489

Gnomad AMR

AF:

0.496

Gnomad ASJ

AF:

0.474

Gnomad EAS

AF:

0.349

Gnomad SAS

AF:

0.419

Gnomad FIN

AF:

0.505

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.524

Gnomad OTH

AF:

0.456

GnomAD3 exomes

AF:

0.480

AC:

120349

AN:

250700

Hom.:

30096

AF XY:

0.483

AC XY:

65398

AN XY:

135502

show subpopulations

Gnomad AFR exome

AF:

0.215

Gnomad AMR exome

AF:

0.537

Gnomad ASJ exome

AF:

0.482

Gnomad EAS exome

AF:

0.357

Gnomad SAS exome

AF:

0.428

Gnomad FIN exome

AF:

0.527

Gnomad NFE exome

AF:

0.524

Gnomad OTH exome

AF:

0.504

GnomAD4 exome

AF:

0.505

AC:

735335

AN:

1455356

Hom.:

189116

Cov.:

AF XY:

0.504

AC XY:

364488

AN XY:

723516

show subpopulations

Gnomad4 AFR exome

AF:

0.211

Gnomad4 AMR exome

AF:

0.538

Gnomad4 ASJ exome

AF:

0.482

Gnomad4 EAS exome

AF:

0.362

Gnomad4 SAS exome

AF:

0.427

Gnomad4 FIN exome

AF:

0.537

Gnomad4 NFE exome

AF:

0.524

Gnomad4 OTH exome

AF:

0.488

GnomAD4 genome

AF:

0.425

AC:

64567

AN:

151964

Hom.:

15123

Cov.:

AF XY:

0.423

AC XY:

31435

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.219

Gnomad4 AMR

AF:

0.496

Gnomad4 ASJ

AF:

0.474

Gnomad4 EAS

AF:

0.349

Gnomad4 SAS

AF:

0.418

Gnomad4 FIN

AF:

0.505

Gnomad4 NFE

AF:

0.524

Gnomad4 OTH

AF:

0.454

Alfa

AF:

0.496

Hom.:

44649

Bravo

AF:

0.418

Asia WGS

AF:

0.355

AC:

1237

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.0

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000020

dbscSNV1_RF

Benign

0.0

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