rs796858947

Variant names:

• chr5-139307139-GTTTTT-G
• rs796858947
• NM_018834.6:c.-177-94_-177-90delTTTTT

Your query was ambiguous. Multiple possible variants found:

• chr5-139307139-GTTTTT-G
• chr5-139307139-GTTTTT-GT
• chr5-139307139-GTTTTT-GTT
• chr5-139307139-GTTTTT-GTTT
• chr5-139307139-GTTTTT-GTTTT
• chr5-139307139-GTTTTT-GTTTTTT
• chr5-139307139-GTTTTT-GTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018834.6(MATR3):​c.-177-94_-177-90delTTTTT variant causes a intron change. The variant allele was found at a frequency of 0.00000679 in 147,288 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 0.0000068 (0 hom., cov: 32)
• Consequence: MATR3 NM_018834.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.09
• Publications: 0 publications found

Genes affected

MATR3 (HGNC:6912): (matrin 3) This gene encodes a nuclear matrix protein, which is proposed to stabilize certain messenger RNA species. Mutations of this gene are associated with distal myopathy 2, which often includes vocal cord and pharyngeal weakness. Alternatively spliced transcript variants, including read-through transcripts composed of the upstream small nucleolar RNA host gene 4 (non-protein coding) and matrin 3 gene sequence, have been identified. Pseudogenes of this gene are located on chromosomes 1 and X. [provided by RefSeq, Aug 2013]

MATR3 Gene-Disease associations (from GenCC):

• distal myopathy with vocal cord weakness

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• amyotrophic lateral sclerosis type 21

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018834.6. 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
	MATR3	NM_018834.6	MANE Select	c.-177-94_-177-90delTTTTT		intron	N/A	NP_061322.2
	MATR3	NM_001400441.1		c.-177-94_-177-90delTTTTT		intron	N/A	NP_001387370.1	A8MXP9
	MATR3	NM_001400442.1		c.-177-94_-177-90delTTTTT		intron	N/A	NP_001387371.1	A8MXP9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATR3	ENST00000394805.8	TSL:1 MANE Select	c.-177-94_-177-90delTTTTT		intron	N/A	ENSP00000378284.3	P43243-1
	MATR3	ENST00000502929.5	TSL:2	c.-177-94_-177-90delTTTTT		intron	N/A	ENSP00000422319.1	A8MXP9
	MATR3	ENST00000618441.5	TSL:1	c.-177-94_-177-90delTTTTT		intron	N/A	ENSP00000482895.1	P43243-1

Frequencies

GnomAD3 genomes AF: 0.00000679 AC: 1 AN: 147288 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000249

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

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00000679 AC: 1 AN: 147288 Hom.: 0 Cov.: 32 AF XY: 0.0000140 AC XY: 1 AN XY: 71670

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

African (AFR) AF: 0.0000249 AC: 1 AN: 40096

American (AMR) AF: 0.00 AC: 0 AN: 14692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3384

East Asian (EAS) AF: 0.00 AC: 0 AN: 5066

South Asian (SAS) AF: 0.00 AC: 0 AN: 4650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66566

Other (OTH) AF: 0.00 AC: 0 AN: 2020

⚠️ 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		4.1

Splicing

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

Other links and lift over

dbSNP: rs796858947; hg19: chr5-138642828;