19-1506308-C-T

Variant names:

• chr19-1506308-C-T
• NM_213604.3:c.1123G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_213604.3(ADAMTSL5):​c.1123G>A​(p.Ala375Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000717 in 1,394,752 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: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ADAMTSL5 NM_213604.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.03

Genes affected

ADAMTSL5 (HGNC:27912): (ADAMTS like 5) Enables heparin binding activity and microfibril binding activity. Located in extracellular region and microfibril. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31147948).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL5	NM_213604.3	c.1123G>A	p.Ala375Thr	missense_variant	Exon 12 of 12	ENST00000330475.9	NP_998769.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL5	ENST00000330475.9	c.1123G>A	p.Ala375Thr	missense_variant	Exon 12 of 12	2	NM_213604.3	ENSP00000327608.3
ADAMTSL5	ENST00000585700.5	n.1121G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 11 of 11	1
ADAMTSL5	ENST00000590440.5	n.1161G>A		non_coding_transcript_exon_variant	Exon 12 of 12	1
ADAMTSL5	ENST00000395467.6	c.350G>A	p.Gly117Asp	missense_variant, splice_region_variant	Exon 11 of 11	5		ENSP00000378850.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1394752 Hom.: 0 Cov.: 32 AF XY: 0.00000146 AC XY: 1 AN XY: 685230

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: 9.29e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	29
DANN	Benign	0.69
DEOGEN2	Benign	0.077	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.87	T
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.13
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.0070	D
Vest4		0.41
MVP		0.48
MPC		0.51
ClinPred		0.61	D
GERP RS		3.4
gMVP		0.61

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: chr19-1506307;