rs587777300

Positions:

• chr5-139307759-T-A
• chr5-139307759-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_018834.6(MATR3):​c.344T>A​(p.Phe115Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F115C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MATR3 NM_018834.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.23

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, MATR3

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MATR3	NM_018834.6	c.344T>A	p.Phe115Tyr	missense_variant	2/15	ENST00000394805.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MATR3	ENST00000394805.8	c.344T>A	p.Phe115Tyr	missense_variant	2/15	1	NM_018834.6	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	34
DANN	Uncertain	0.99
DEOGEN2	Benign	0.094	T;T;T;T;T;.;T;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.49	T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.20	D
MutationAssessor	Benign	1.4	L;L;.;.;L;.;.;L
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.020	N;N;N;N;N;N;N;.
REVEL	Uncertain	0.46
Sift	Uncertain	0.0060	D;D;D;D;D;D;D;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;T;D;D
Polyphen		0.98	D;D;P;P;D;.;D;D
Vest4		0.62
MutPred		0.38		Gain of catalytic residue at F115 (P = 0.064);Gain of catalytic residue at F115 (P = 0.064);Gain of catalytic residue at F115 (P = 0.064);Gain of catalytic residue at F115 (P = 0.064);Gain of catalytic residue at F115 (P = 0.064);Gain of catalytic residue at F115 (P = 0.064);Gain of catalytic residue at F115 (P = 0.064);Gain of catalytic residue at F115 (P = 0.064);
MVP		0.89
MPC		2.1
ClinPred		0.79	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.40
gMVP		0.57

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: rs587777300; hg19: chr5-138643448;