chr5-139307430-C-G

Variant names:

• chr5-139307430-C-G
• NM_018834.6:c.15C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018834.6(MATR3):​c.15C>G​(p.Phe5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MATR3 NM_018834.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28497076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MATR3	NM_018834.6	c.15C>G	p.Phe5Leu	missense_variant	Exon 2 of 15	ENST00000394805.8	NP_061322.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MATR3	ENST00000394805.8	c.15C>G	p.Phe5Leu	missense_variant	Exon 2 of 15	1	NM_018834.6	ENSP00000378284.3
MATR3	ENST00000394800.6	c.15C>G	p.Phe5Leu	missense_variant	Exon 6 of 19	5		ENSP00000378279.2
MATR3	ENST00000502929.5	c.15C>G	p.Phe5Leu	missense_variant	Exon 7 of 20	2		ENSP00000422319.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461730 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727184

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	34
DANN	Uncertain	0.99
DEOGEN2	Benign	0.051	T;T;.;T;T;T;.;T;.;T;T;.;.;T;.;.
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.91	.;.;D;.;D;D;D;.;D;D;D;D;D;D;D;D
M_CAP	Uncertain	0.095	D
MetaRNN	Benign	0.28	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.090	T
MutationAssessor	Benign	0.34	N;N;.;.;.;.;.;N;.;.;N;.;.;.;.;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	0.40	N;N;D;N;N;D;D;N;N;N;.;D;D;D;D;.
REVEL	Uncertain	0.43
Sift	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;D;.;D;D;D;D;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;T
Polyphen		0.96	P;P;.;B;B;.;.;P;.;P;P;.;.;.;.;.
Vest4		0.55
MutPred		0.090		Loss of methylation at K3 (P = 0.0923);Loss of methylation at K3 (P = 0.0923);Loss of methylation at K3 (P = 0.0923);Loss of methylation at K3 (P = 0.0923);Loss of methylation at K3 (P = 0.0923);Loss of methylation at K3 (P = 0.0923);Loss of methylation at K3 (P = 0.0923);Loss of methylation at K3 (P = 0.0923);Loss of methylation at K3 (P = 0.0923);Loss of methylation at K3 (P = 0.0923);Loss of methylation at K3 (P = 0.0923);Loss of methylation at K3 (P = 0.0923);Loss of methylation at K3 (P = 0.0923);Loss of methylation at K3 (P = 0.0923);Loss of methylation at K3 (P = 0.0923);Loss of methylation at K3 (P = 0.0923);
MVP		0.84
MPC		2.1
ClinPred		0.74	D
GERP RS		4.8
Varity_R		0.55
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-138643119;