13-29324646-C-T

Position:

• chr13-29324646-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001033602.4(MTUS2):​c.2840C>T​(p.Thr947Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 1,594,210 control chromosomes in the GnomAD database, including 879 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.025 (69 hom., cov: 34)
  • Exomes 𝑓: 0.031 (810 hom.)
• Consequence: MTUS2 NM_001033602.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.524

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024681985).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.025 (3813/152308) while in subpopulation NFE AF= 0.0346 (2355/68024). AF 95% confidence interval is 0.0335. There are 69 homozygotes in gnomad4. There are 1852 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 69 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTUS2	NM_001033602.4	c.2840C>T	p.Thr947Met	missense_variant	7/16	ENST00000612955.6	NP_001028774.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTUS2	ENST00000612955.6	c.2840C>T	p.Thr947Met	missense_variant	7/16	5	NM_001033602.4	ENSP00000483729

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 3814 AN: 152190 Hom.: 69 Cov.: 34

Gnomad AFR AF: 0.00820

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0198

Gnomad ASJ AF: 0.0715

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.0343

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0346

Gnomad OTH AF: 0.0310

GnomAD3 exomes AF: 0.0279 AC: 6132 AN: 219886 Hom.: 116 AF XY: 0.0284 AC XY: 3348 AN XY: 117818

Gnomad AFR exome AF: 0.00880

Gnomad AMR exome AF: 0.0147

Gnomad ASJ exome AF: 0.0768

Gnomad EAS exome AF: 0.000123

Gnomad SAS exome AF: 0.0263

Gnomad FIN exome AF: 0.0344

Gnomad NFE exome AF: 0.0336

Gnomad OTH exome AF: 0.0307

GnomAD4 exome AF: 0.0308 AC: 44444 AN: 1441902 Hom.: 810 Cov.: 34 AF XY: 0.0308 AC XY: 22025 AN XY: 714902

Gnomad4 AFR exome AF: 0.00872

Gnomad4 AMR exome AF: 0.0148

Gnomad4 ASJ exome AF: 0.0755

Gnomad4 EAS exome AF: 0.0000509

Gnomad4 SAS exome AF: 0.0266

Gnomad4 FIN exome AF: 0.0347

Gnomad4 NFE exome AF: 0.0323

Gnomad4 OTH exome AF: 0.0308

GnomAD4 genome AF: 0.0250 AC: 3813 AN: 152308 Hom.: 69 Cov.: 34 AF XY: 0.0249 AC XY: 1852 AN XY: 74478

Gnomad4 AFR AF: 0.00825

Gnomad4 AMR AF: 0.0198

Gnomad4 ASJ AF: 0.0715

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0255

Gnomad4 FIN AF: 0.0343

Gnomad4 NFE AF: 0.0346

Gnomad4 OTH AF: 0.0307

Alfa AF: 0.0315 Hom.: 138

Bravo AF: 0.0235

TwinsUK AF: 0.0348 AC: 129

ALSPAC AF: 0.0337 AC: 130

ESP6500AA AF: 0.00829 AC: 31

ESP6500EA AF: 0.0376 AC: 308

ExAC AF: 0.0258 AC: 3114

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	15
DANN	Uncertain	0.99
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
Sift4G	Uncertain	0.011	D
Vest4		0.042
ClinPred		0.018	T
GERP RS		3.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs61999321; hg19: chr13-29898783; COSMIC: COSV70913982;