13-29487954-C-G

Position:

• chr13-29487954-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001033602.4(MTUS2):​c.3454C>G​(p.His1152Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTUS2 NM_001033602.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.92

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.849

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTUS2	NM_001033602.4	c.3454C>G	p.His1152Asp	missense_variant	11/16	ENST00000612955.6	NP_001028774.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTUS2	ENST00000612955.6	c.3454C>G	p.His1152Asp	missense_variant	11/16	5	NM_001033602.4	ENSP00000483729.2
MTUS2	ENST00000380808.6	c.391C>G	p.His131Asp	missense_variant	4/9	1		ENSP00000370186.2
MTUS2	ENST00000542829.1	c.121C>G	p.His41Asp	missense_variant	3/8	1		ENSP00000445403.1
MTUS2-AS1	ENST00000323380.7	n.675G>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

Sep 04, 2024

The c.3484C>G (p.H1162D) 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 3484, causing the histidine (H) at amino acid position 1162 to be replaced by an aspartic acid (D). 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	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	27
DANN	Uncertain	0.99
Eigen	Uncertain	0.36
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.85	D;D;D
MetaSVM	Benign	-0.89	T
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-7.7	.;D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0050	.;D;D
Sift4G	Uncertain	0.025	D;T;T
Polyphen		0.99	.;D;.
Vest4		0.87
MVP		0.23
ClinPred		0.98	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: chr13-30062091;