5-5140672-G-A

Variant names:

• chr5-5140672-G-A
• NM_139056.4:c.81G>A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_139056.4(ADAMTS16):​c.81G>A​(p.Ala27Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000499 in 1,402,030 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: ADAMTS16 NM_139056.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414

Genes affected

ADAMTS16 (HGNC:17108): (ADAM metallopeptidase with thrombospondin type 1 motif 16) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. ADAMTS family members 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 protein, which may inhibit chondrosarcoma cell proliferation and migration. This gene may regulate blood pressure. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP7: Synonymous conserved (PhyloP=0.414 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS16	NM_139056.4	c.81G>A	p.Ala27Ala	synonymous_variant	Exon 2 of 23	ENST00000274181.7	NP_620687.2
ADAMTS16	XM_047416874.1	c.81G>A	p.Ala27Ala	synonymous_variant	Exon 2 of 22		XP_047272830.1
ADAMTS16	XM_047416875.1	c.81G>A	p.Ala27Ala	synonymous_variant	Exon 2 of 20		XP_047272831.1
ADAMTS16	NR_136935.2	n.219G>A		non_coding_transcript_exon_variant	Exon 2 of 22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS16	ENST00000274181.7	c.81G>A	p.Ala27Ala	synonymous_variant	Exon 2 of 23	2	NM_139056.4	ENSP00000274181.7
ADAMTS16	ENST00000511368.5	c.81G>A	p.Ala27Ala	synonymous_variant	Exon 2 of 11	1		ENSP00000421631.1
ADAMTS16	ENST00000433402.2	n.81G>A		non_coding_transcript_exon_variant	Exon 2 of 20	1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000499 AC: 7 AN: 1402030 Hom.: 0 Cov.: 34 AF XY: 0.00000577 AC XY: 4 AN XY: 692718

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000553

Gnomad4 OTH exome AF: 0.0000171

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	12
DANN	Uncertain	0.98

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-5140785;