13-29487974-C-G

Variant names:

• chr13-29487974-C-G
• rs1329463819
• NM_001033602.4:c.3474C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001033602.4(MTUS2):​c.3474C>G​(p.Ile1158Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: MTUS2 NM_001033602.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0240
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16196063).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033602.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTUS2	NM_001033602.4	MANE Select	c.3474C>G	p.Ile1158Met	missense	Exon 11 of 16	NP_001028774.3	Q5JR59-2
	MTUS2	NM_001384605.1		c.3474C>G	p.Ile1158Met	missense	Exon 11 of 16	NP_001371534.1	Q5JR59-2
	MTUS2	NM_001384606.1		c.3474C>G	p.Ile1158Met	missense	Exon 10 of 15	NP_001371535.1	Q5JR59-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTUS2	ENST00000612955.6	TSL:5 MANE Select	c.3474C>G	p.Ile1158Met	missense	Exon 11 of 16	ENSP00000483729.2	Q5JR59-2
	MTUS2	ENST00000380808.6	TSL:1	c.411C>G	p.Ile137Met	missense	Exon 4 of 9	ENSP00000370186.2	Q5JR59-3
	MTUS2	ENST00000542829.1	TSL:1	c.141C>G	p.Ile47Met	missense	Exon 3 of 8	ENSP00000445403.1	Q5JR59-4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000198 AC: 29 AN: 1461804 Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11 AN XY: 727210

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000261 AC: 29 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74356

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Benign	0.15
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.024
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.051
Sift	Benign	0.092	T
Sift4G	Uncertain	0.044	D
Polyphen		0.90	P
Vest4		0.37
MVP		0.076
ClinPred		0.72	D
GERP RS		4.0
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs1329463819; hg19: chr13-30062111;