1-150553568-G-T

Position:

• chr1-150553568-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019032.6(ADAMTSL4):​c.577G>T​(p.Ala193Ser) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A193P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 28)
• Consequence: ADAMTSL4 NM_019032.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

Genes affected

ADAMTSL4 (HGNC:19706): (ADAMTS like 4) This gene is a member of ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs)-like gene family and encodes a protein with seven thrombospondin type 1 repeats. The thrombospondin type 1 repeat domain is found in many proteins with diverse biological functions including cellular adhesion, angiogenesis, and patterning of the developing nervous system. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Sep 2014]

ADAMTSL4-AS2 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038508743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTSL4	NM_019032.6	c.577G>T	p.Ala193Ser	missense_variant	6/19	ENST00000271643.9	NP_061905.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTSL4	ENST00000271643.9	c.577G>T	p.Ala193Ser	missense_variant	6/19	5	NM_019032.6	ENSP00000271643.4

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 73

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.014
DANN	Benign	0.62
DEOGEN2	Benign	0.00024	T;.;.;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.15	.;T;T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.039	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N;N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.040	N;N;N;N
REVEL	Benign	0.019
Sift	Benign	0.32	T;T;T;T
Sift4G	Benign	0.68	T;T;T;T
Polyphen		0.0020	B;.;B;B
Vest4		0.053
MutPred		0.098		Gain of phosphorylation at A193 (P = 0.0039);Gain of phosphorylation at A193 (P = 0.0039);Gain of phosphorylation at A193 (P = 0.0039);Gain of phosphorylation at A193 (P = 0.0039);
MVP		0.42
MPC		0.11
ClinPred		0.14	T
GERP RS		-4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.036
gMVP		0.23

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: rs41317515; hg19: chr1-150526044;