1-150560870-C-T

Variant names:

• chr1-150560870-C-T
• rs886045272
• NM_019032.6:c.*674C>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.*674C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADAMTSL4 NM_019032.6 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.56
• Publications: 0 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-AS1 (HGNC:32041): (ADAMTSL4 antisense RNA 1)

ENSG00000289457 (HGNC:):

MCL1 (HGNC:6943): (MCL1 apoptosis regulator, BCL2 family member) This gene encodes an anti-apoptotic protein, which is a member of the Bcl-2 family. Alternative splicing results in multiple transcript variants. The longest gene product (isoform 1) enhances cell survival by inhibiting apoptosis while the alternatively spliced shorter gene products (isoform 2 and isoform 3) promote apoptosis and are death-inducing. [provided by RefSeq, Oct 2010]

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 (BayesDel_noAF=-0.74).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL4	NM_019032.6	MANE Select	c.*674C>T		3_prime_UTR	Exon 19 of 19	NP_061905.2
	ADAMTSL4	NM_001288608.2		c.*674C>T		3_prime_UTR	Exon 20 of 20	NP_001275537.1	Q6UY14-3
	ADAMTSL4	NM_001378596.1		c.*674C>T		3_prime_UTR	Exon 19 of 19	NP_001365525.1	Q6UY14-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL4	ENST00000271643.9	TSL:5 MANE Select	c.*674C>T		3_prime_UTR	Exon 19 of 19	ENSP00000271643.4	Q6UY14-1
	ADAMTSL4	ENST00000369038.6	TSL:1	c.*674C>T		3_prime_UTR	Exon 17 of 17	ENSP00000358034.2	Q6UY14-1
	ADAMTSL4	ENST00000369039.9	TSL:5	c.*674C>T		3_prime_UTR	Exon 20 of 20	ENSP00000358035.5	Q6UY14-3

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152012 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6300 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 3646

African (AFR) AF: 0.00 AC: 0 AN: 30

American (AMR) AF: 0.00 AC: 0 AN: 802

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 58

East Asian (EAS) AF: 0.00 AC: 0 AN: 90

South Asian (SAS) AF: 0.00 AC: 0 AN: 1606

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 8

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 3330

Other (OTH) AF: 0.00 AC: 0 AN: 244

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152130 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74370

African (AFR) AF: 0.00 AC: 0 AN: 41514

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67974

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000453

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Ectopia lentis 2, isolated, autosomal recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	10
DANN	Benign	0.62
PhyloP100		1.6

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: rs886045272; hg19: chr1-150533346;