5-139307044-ATAC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_018834.6(MATR3):c.-177-190_-177-188del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 152,294 control chromosomes in the GnomAD database, including 86 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.028 (86 hom., cov: 32)
• Consequence: MATR3 NM_018834.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.18

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 5-139307044-ATAC-A is Benign according to our data. Variant chr5-139307044-ATAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 1212042.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.028 (4262/152294) while in subpopulation NFE AF= 0.0473 (3218/68014). AF 95% confidence interval is 0.0459. There are 86 homozygotes in gnomad4. There are 1908 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 4264 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MATR3	NM_018834.6	c.-177-190_-177-188del		intron_variant		ENST00000394805.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MATR3	ENST00000394805.8	c.-177-190_-177-188del		intron_variant		1	NM_018834.6	P1

Frequencies

GnomAD3 genomes AF: 0.0280 AC: 4264 AN: 152176 Hom.: 86 Cov.: 32

Gnomad AFR AF: 0.00862

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0280

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0473

Gnomad OTH AF: 0.0196

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

GnomAD4 genome AF: 0.0280 AC: 4262 AN: 152294 Hom.: 86 Cov.: 32 AF XY: 0.0256 AC XY: 1908 AN XY: 74490

Gnomad4 AFR AF: 0.00859

Gnomad4 AMR AF: 0.0143

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0153

Gnomad4 FIN AF: 0.0280

Gnomad4 NFE AF: 0.0473

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0324 Hom.: 17

Bravo AF: 0.0257

Asia WGS AF: 0.00840 AC: 29 AN: 3468

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 21, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs144702367; hg19: chr5-138642733;