NM_019032.6:c.-84-300_-84-299delAA

Variant names:

• chr1-150551891-CAA-C
• rs199813152
• NM_019032.6:c.-84-300_-84-299delAA

Variant summary

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

The NM_019032.6(ADAMTSL4):​c.-84-300_-84-299delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00737 in 117,990 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 0.00021 (0 hom., cov: 30)
  • Exomes 𝑓: 0.034 (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.-84-300_-84-299delAA		intron	N/A	NP_061905.2
	ADAMTSL4	NM_001288608.2		c.-84-300_-84-299delAA		intron	N/A	NP_001275537.1	Q6UY14-3
	ADAMTSL4	NM_001378596.1		c.-84-300_-84-299delAA		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.-84-322_-84-321delAA		intron	N/A	ENSP00000271643.4	Q6UY14-1
	ADAMTSL4	ENST00000483335.1	TSL:1	n.1803_1804delAA		non_coding_transcript_exon	Exon 3 of 3
	ADAMTSL4	ENST00000369039.9	TSL:5	c.-84-322_-84-321delAA		intron	N/A	ENSP00000358035.5	Q6UY14-3

Frequencies

GnomAD3 genomes AF: 0.000205 AC: 19 AN: 92596 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000379

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000233

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00255

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000945

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0187 AC: 71 AN: 3788 AF XY: 0.0242

Gnomad AFR exome AF: 0.00877

Gnomad AMR exome AF: 0.0467

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad NFE exome AF: 0.0155

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0335 AC: 851 AN: 25374 Hom.: 0 AF XY: 0.0335 AC XY: 437 AN XY: 13054

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

African (AFR) AF: 0.0260 AC: 20 AN: 770

American (AMR) AF: 0.0466 AC: 58 AN: 1244

Ashkenazi Jewish (ASJ) AF: 0.0325 AC: 30 AN: 922

East Asian (EAS) AF: 0.0335 AC: 50 AN: 1494

South Asian (SAS) AF: 0.0413 AC: 42 AN: 1016

European-Finnish (FIN) AF: 0.0246 AC: 31 AN: 1260

Middle Eastern (MID) AF: 0.00851 AC: 4 AN: 470

European-Non Finnish (NFE) AF: 0.0339 AC: 562 AN: 16556

Other (OTH) AF: 0.0329 AC: 54 AN: 1642

⚠️ 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: 0.000205 AC: 19 AN: 92616 Hom.: 0 Cov.: 30 AF XY: 0.000183 AC XY: 8 AN XY: 43676

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

African (AFR) AF: 0.0000378 AC: 1 AN: 26454

American (AMR) AF: 0.000233 AC: 2 AN: 8592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2322

East Asian (EAS) AF: 0.00 AC: 0 AN: 3292

South Asian (SAS) AF: 0.00 AC: 0 AN: 3036

European-Finnish (FIN) AF: 0.00255 AC: 12 AN: 4710

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 168

European-Non Finnish (NFE) AF: 0.0000945 AC: 4 AN: 42322

Other (OTH) AF: 0.00 AC: 0 AN: 1198

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

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: rs199813152; hg19: chr1-150524367;