13-29487975-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001033602.4(MTUS2):c.3475C>G(p.Leu1159Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTUS2 NM_001033602.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.30

Genes affected

MTUS2 (HGNC:20595): (microtubule associated scaffold protein 2) Enables microtubule binding activity and protein homodimerization activity. Part of nucleus. Colocalizes with centrosome and cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

MTUS2-AS1 (HGNC:40924): (MTUS2 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTUS2	NM_001033602.4	c.3475C>G	p.Leu1159Val	missense_variant	11/16	ENST00000612955.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTUS2	ENST00000612955.6	c.3475C>G	p.Leu1159Val	missense_variant	11/16	5	NM_001033602.4
MTUS2	ENST00000380808.6	c.412C>G	p.Leu138Val	missense_variant	4/9	1		P1
MTUS2	ENST00000542829.1	c.142C>G	p.Leu48Val	missense_variant	3/8	1
MTUS2-AS1	ENST00000323380.7	n.654G>C		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.3505C>G (p.L1169V) alteration is located in exon 9 (coding exon 9) of the MTUS2 gene. This alteration results from a C to G substitution at nucleotide position 3505, causing the leucine (L) at amino acid position 1169 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.85	D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Benign	-0.89	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.55	T
Sift4G	Benign	0.086	T;T;T
Polyphen		0.99	.;D;.
Vest4		0.65
MVP		0.40
ClinPred		0.97	D
GERP RS		4.0

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: chr13-30062112;