19-1506644-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_213604.3(ADAMTSL5):​c.1060C>T​(p.Pro354Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict 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)

Consequence

ADAMTSL5
NM_213604.3 missense

Scores

3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.46
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17570269).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADAMTSL5NM_213604.3 linkc.1060C>T p.Pro354Ser missense_variant Exon 11 of 12 ENST00000330475.9 NP_998769.2 Q6ZMM2Q0VD77X6R4H8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADAMTSL5ENST00000330475.9 linkc.1060C>T p.Pro354Ser missense_variant Exon 11 of 12 2 NM_213604.3 ENSP00000327608.3 X6R4H8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
52
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000312
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 25, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1060C>T (p.P354S) alteration is located in exon 11 (coding exon 10) of the ADAMTSL5 gene. This alteration results from a C to T substitution at nucleotide position 1060, causing the proline (P) at amino acid position 354 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0076
T
Eigen
Benign
-0.25
Eigen_PC
Benign
-0.19
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.65
T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-1.1
T
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.029
Sift
Benign
0.071
T
Sift4G
Benign
0.088
T
Vest4
0.33
MVP
0.33
MPC
0.21
ClinPred
0.46
T
GERP RS
4.1
gMVP
0.27

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs1912941519; hg19: chr19-1506643; API