1-150553568-G-T

Variant names:

• chr1-150553568-G-T
• rs41317515
• NM_019032.6:c.577G>T

Variant summary

Our verdict is Likely benign. The variant received -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. 17/22 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
• Publications: 36 publications found

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:40895): (ADAMTSL4 antisense RNA 2)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019032.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL4	NM_019032.6	MANE Select	c.577G>T	p.Ala193Ser	missense	Exon 6 of 19	NP_061905.2
	ADAMTSL4	NM_001288608.2		c.577G>T	p.Ala193Ser	missense	Exon 6 of 20	NP_001275537.1
	ADAMTSL4	NM_001378596.1		c.577G>T	p.Ala193Ser	missense	Exon 6 of 19	NP_001365525.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL4	ENST00000271643.9	TSL:5 MANE Select	c.577G>T	p.Ala193Ser	missense	Exon 6 of 19	ENSP00000271643.4
	ADAMTSL4	ENST00000369038.6	TSL:1	c.577G>T	p.Ala193Ser	missense	Exon 4 of 17	ENSP00000358034.2
	ADAMTSL4	ENST00000369039.9	TSL:5	c.577G>T	p.Ala193Ser	missense	Exon 6 of 20	ENSP00000358035.5

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 73

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-1.2
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.019
Sift	Benign	0.32	T
Sift4G	Benign	0.68	T
Polyphen		0.0020	B
Vest4		0.053
MutPred		0.098		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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs41317515; hg19: chr1-150526044;