1-150551891-CAAAAAAA-CAAAAAAAAAA

Variant names:

• chr1-150551891-C-CAAA
• rs199813152
• NM_019032.6:c.-84-301_-84-299dupAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_019032.6(ADAMTSL4):​c.-84-301_-84-299dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000758 in 118,680 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000075 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000077 (0 hom.)
• Consequence: ADAMTSL4 NM_019032.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.855
• 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-AS2 (HGNC:40895): (ADAMTSL4 antisense RNA 2)

MIR4257 (HGNC:38312): (microRNA 4257) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.-84-301_-84-299dupAAA		intron	N/A	NP_061905.2
	ADAMTSL4	NM_001288608.2		c.-84-301_-84-299dupAAA		intron	N/A	NP_001275537.1	Q6UY14-3
	ADAMTSL4	NM_001378596.1		c.-84-301_-84-299dupAAA		intron	N/A	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.-84-321_-84-320insAAA		intron	N/A	ENSP00000271643.4	Q6UY14-1
	ADAMTSL4	ENST00000483335.1	TSL:1	n.1804_1805insAAA		non_coding_transcript_exon	Exon 3 of 3
	ADAMTSL4	ENST00000369039.9	TSL:5	c.-84-321_-84-320insAAA		intron	N/A	ENSP00000358035.5	Q6UY14-3

Frequencies

GnomAD3 genomes AF: 0.0000755 AC: 7 AN: 92726 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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 AF: 0.0000771 AC: 2 AN: 25954 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 13350

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00129 AC: 1 AN: 776

American (AMR) AF: 0.00 AC: 0 AN: 1274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 938

East Asian (EAS) AF: 0.00 AC: 0 AN: 1526

South Asian (SAS) AF: 0.00 AC: 0 AN: 1036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 476

European-Non Finnish (NFE) AF: 0.0000589 AC: 1 AN: 16966

Other (OTH) AF: 0.00 AC: 0 AN: 1672

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000755 AC: 7 AN: 92726 Hom.: 0 Cov.: 30 AF XY: 0.000114 AC XY: 5 AN XY: 43718

African (AFR) AF: 0.000265 AC: 7 AN: 26420

American (AMR) AF: 0.00 AC: 0 AN: 8594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2326

East Asian (EAS) AF: 0.00 AC: 0 AN: 3298

South Asian (SAS) AF: 0.00 AC: 0 AN: 3056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4762

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 180

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 42380

Other (OTH) AF: 0.00 AC: 0 AN: 1188

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.85
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs199813152; hg19: chr1-150524367;