8-17693345-A-G

Position:

• chr8-17693345-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001363059.2(MTUS1):​c.2624-8803T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 151,952 control chromosomes in the GnomAD database, including 5,685 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (5684 hom., cov: 32)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: MTUS1 NM_001363059.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTUS1	NM_001363059.2	c.2624-8803T>C		intron_variant		ENST00000693296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTUS1	ENST00000693296.1	c.2624-8803T>C		intron_variant			NM_001363059.2

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39984 AN: 151830 Hom.: 5680 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.300

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.750 AC XY: 3 AN XY: 4

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.263 AC: 40002 AN: 151948 Hom.: 5684 Cov.: 32 AF XY: 0.269 AC XY: 19952 AN XY: 74236

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.297

Alfa AF: 0.277 Hom.: 12353

Bravo AF: 0.262

Asia WGS AF: 0.400 AC: 1386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.029
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs209973; hg19: chr8-17550854;