chr8-17653257-C-G

Position:

• chr8-17653257-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001363059.2(MTUS1):​c.3313G>C​(p.Glu1105Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00764 in 1,557,832 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0077 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0076 (61 hom.)
• Consequence: MTUS1 NM_001363059.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.82

Genes affected

MTUS1 (HGNC:29789): (microtubule associated scaffold protein 1) This gene encodes a protein which contains a C-terminal domain able to interact with the angiotension II (AT2) receptor and a large coiled-coil region allowing dimerization. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. One of the transcript variants has been shown to encode a mitochondrial protein that acts as a tumor suppressor and partcipates in AT2 signaling pathways. Other variants may encode nuclear or transmembrane proteins but it has not been determined whether they also participate in AT2 signaling pathways. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007748425).
• BP6: Variant 8-17653257-C-G is Benign according to our data. Variant chr8-17653257-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2658445.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00763 (10720/1405544) while in subpopulation MID AF= 0.0221 (125/5660). AF 95% confidence interval is 0.0189. There are 61 homozygotes in gnomad4_exome. There are 5272 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 61 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTUS1	NM_001363059.2	c.3313G>C	p.Glu1105Gln	missense_variant	12/15	ENST00000693296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTUS1	ENST00000693296.1	c.3313G>C	p.Glu1105Gln	missense_variant	12/15		NM_001363059.2

Frequencies

GnomAD3 genomes AF: 0.00766 AC: 1166 AN: 152170 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00794

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00635

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.00871

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00950

Gnomad OTH AF: 0.00813

GnomAD3 exomes AF: 0.00594 AC: 1092 AN: 183926 Hom.: 6 AF XY: 0.00579 AC XY: 577 AN XY: 99654

Gnomad AFR exome AF: 0.00692

Gnomad AMR exome AF: 0.00470

Gnomad ASJ exome AF: 0.00543

Gnomad EAS exome AF: 0.00224

Gnomad SAS exome AF: 0.00595

Gnomad FIN exome AF: 0.000560

Gnomad NFE exome AF: 0.00786

Gnomad OTH exome AF: 0.00750

GnomAD4 exome AF: 0.00763 AC: 10720 AN: 1405544 Hom.: 61 Cov.: 29 AF XY: 0.00756 AC XY: 5272 AN XY: 696984

Gnomad4 AFR exome AF: 0.00626

Gnomad4 AMR exome AF: 0.00504

Gnomad4 ASJ exome AF: 0.00485

Gnomad4 EAS exome AF: 0.00217

Gnomad4 SAS exome AF: 0.00592

Gnomad4 FIN exome AF: 0.000902

Gnomad4 NFE exome AF: 0.00830

Gnomad4 OTH exome AF: 0.00877

GnomAD4 genome AF: 0.00772 AC: 1175 AN: 152288 Hom.: 1 Cov.: 32 AF XY: 0.00739 AC XY: 550 AN XY: 74466

Gnomad4 AFR AF: 0.00809

Gnomad4 AMR AF: 0.00634

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.00913

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00950

Gnomad4 OTH AF: 0.00805

Alfa AF: 0.00892 Hom.: 10

Bravo AF: 0.00783

TwinsUK AF: 0.0105 AC: 39

ALSPAC AF: 0.00727 AC: 28

ESP6500AA AF: 0.00745 AC: 27

ESP6500EA AF: 0.00785 AC: 64

ExAC AF: 0.00474 AC: 570

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

MTUS1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	.;.;.;.;T;.;.
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D;D;D;D;D;.;D
MetaRNN	Benign	0.0077	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.86	.;.;.;.;L;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.8	N;N;N;N;N;N;.
REVEL	Benign	0.19
Sift	Benign	0.67	T;T;T;T;T;T;.
Sift4G	Benign	0.47	T;T;T;T;T;T;T
Polyphen		0.94, 1.0, 0.97	.;P;D;D;P;P;.
Vest4		0.52
MVP		0.57
ClinPred		0.039	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.23
gMVP		0.37

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

LitVar

Other links and lift over

dbSNP: rs61733705; hg19: chr8-17510766; COSMIC: COSV99030014; COSMIC: COSV99030014;