10-70708643-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_080722.4(ADAMTS14):c.735C>T(p.Gly245=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,612,772 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0075 (18 hom., cov: 31)
  • Exomes 𝑓: 0.00086 (16 hom.)
• Consequence: ADAMTS14 NM_080722.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.35

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 10-70708643-C-T is Benign according to our data. Variant chr10-70708643-C-T is described in ClinVar as [Benign]. Clinvar id is 788428.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.35 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0075 (1141/152150) while in subpopulation AFR AF= 0.026 (1079/41496). AF 95% confidence interval is 0.0247. There are 18 homozygotes in gnomad4. There are 564 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTS14	NM_080722.4	c.735C>T	p.Gly245=	synonymous_variant	4/22	ENST00000373207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTS14	ENST00000373207.2	c.735C>T	p.Gly245=	synonymous_variant	4/22	1	NM_080722.4	P4
ADAMTS14	ENST00000373208.5	c.735C>T	p.Gly245=	synonymous_variant	4/22	2		A2

Frequencies

GnomAD3 genomes AF: 0.00748 AC: 1137 AN: 152032 Hom.: 18 Cov.: 31

Gnomad AFR AF: 0.0260

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00194 AC: 486 AN: 250858 Hom.: 8 AF XY: 0.00144 AC XY: 196 AN XY: 135688

Gnomad AFR exome AF: 0.0265

Gnomad AMR exome AF: 0.000666

Gnomad ASJ exome AF: 0.000696

Gnomad EAS exome AF: 0.000490

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000816

GnomAD4 exome AF: 0.000858 AC: 1253 AN: 1460622 Hom.: 16 Cov.: 32 AF XY: 0.000746 AC XY: 542 AN XY: 726454

Gnomad4 AFR exome AF: 0.0289

Gnomad4 AMR exome AF: 0.00101

Gnomad4 ASJ exome AF: 0.000995

Gnomad4 EAS exome AF: 0.000756

Gnomad4 SAS exome AF: 0.0000928

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000621

Gnomad4 OTH exome AF: 0.00174

GnomAD4 genome AF: 0.00750 AC: 1141 AN: 152150 Hom.: 18 Cov.: 31 AF XY: 0.00758 AC XY: 564 AN XY: 74386

Gnomad4 AFR AF: 0.0260

Gnomad4 AMR AF: 0.00288

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.000582

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00330 Hom.: 2

Bravo AF: 0.00895

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 25, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.36
Dann	Benign	0.81
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

Other links and lift over

dbSNP: rs114865808; hg19: chr10-72468399;