rs182740

Variant names:

• chr13-29025692-C-T
• rs182740
• NM_001033602.4:c.994C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001033602.4(MTUS2):​c.994C>T​(p.Leu332Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00373 in 1,613,980 control chromosomes in the GnomAD database, including 193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (97 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (96 hom.)
• Consequence: MTUS2 NM_001033602.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.706
• Publications: 2 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]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 13-29025692-C-T is Benign according to our data. Variant chr13-29025692-C-T is described in ClinVar as Benign. ClinVar VariationId is 790671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.706 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0656 is higher than 0.05.

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.994C>T	p.Leu332Leu	synonymous	Exon 3 of 16	NP_001028774.3	Q5JR59-2
	MTUS2	NM_001384605.1		c.994C>T	p.Leu332Leu	synonymous	Exon 3 of 16	NP_001371534.1	Q5JR59-2
	MTUS2	NM_001384606.1		c.994C>T	p.Leu332Leu	synonymous	Exon 2 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.994C>T	p.Leu332Leu	synonymous	Exon 3 of 16	ENSP00000483729.2	Q5JR59-2
	MTUS2	ENST00000948542.1		c.994C>T	p.Leu332Leu	synonymous	Exon 3 of 16	ENSP00000618601.1

Frequencies

GnomAD3 genomes AF: 0.0199 AC: 3024 AN: 152178 Hom.: 95 Cov.: 32

Gnomad AFR AF: 0.0677

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00520 AC: 1293 AN: 248680 AF XY: 0.00398

Gnomad AFR exome AF: 0.0717

Gnomad AMR exome AF: 0.00339

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000622

Gnomad OTH exome AF: 0.00315

GnomAD4 exome AF: 0.00205 AC: 2994 AN: 1461684 Hom.: 96 Cov.: 31 AF XY: 0.00175 AC XY: 1272 AN XY: 727120

African (AFR) AF: 0.0692 AC: 2315 AN: 33476

American (AMR) AF: 0.00438 AC: 196 AN: 44722

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

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

South Asian (SAS) AF: 0.000974 AC: 84 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00295 AC: 17 AN: 5768

European-Non Finnish (NFE) AF: 0.0000773 AC: 86 AN: 1111864

Other (OTH) AF: 0.00490 AC: 296 AN: 60374

GnomAD4 genome AF: 0.0199 AC: 3033 AN: 152296 Hom.: 97 Cov.: 32 AF XY: 0.0193 AC XY: 1434 AN XY: 74474

African (AFR) AF: 0.0677 AC: 2813 AN: 41532

American (AMR) AF: 0.0115 AC: 176 AN: 15304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68032

Other (OTH) AF: 0.0114 AC: 24 AN: 2114

Alfa AF: 0.00835 Hom.: 25

Bravo AF: 0.0230

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.42
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs182740; hg19: chr13-29599829;