chr8-124700179-G-A

Variant names:

• chr8-124700179-G-A
• rs10956197
• NM_014751.6:c.135-580C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014751.6(MTSS1):​c.135-580C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 151,348 control chromosomes in the GnomAD database, including 39,925 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 0.73 (39925 hom., cov: 29)
• Consequence: MTSS1 NM_014751.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286
• Publications: 5 publications found

Genes affected

MTSS1 (HGNC:20443): (MTSS I-BAR domain containing 1) Enables actin monomer binding activity; identical protein binding activity; and signaling receptor binding activity. Predicted to be involved in cellular response to fluid shear stress; negative regulation of epithelial cell proliferation; and urogenital system development. Predicted to act upstream of or within several processes, including actin filament polymerization; adherens junction maintenance; and magnesium ion homeostasis. Located in actin cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTSS1	NM_014751.6	c.135-580C>T		intron_variant	Intron 2 of 13	ENST00000518547.6	NP_055566.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTSS1	ENST00000518547.6	c.135-580C>T		intron_variant	Intron 2 of 13	1	NM_014751.6	ENSP00000429064.1

Frequencies

GnomAD3 genomes AF: 0.726 AC: 109800 AN: 151238 Hom.: 39901 Cov.: 29

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.766

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.682

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.726

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.726 AC: 109876 AN: 151348 Hom.: 39925 Cov.: 29 AF XY: 0.727 AC XY: 53715 AN XY: 73862

African (AFR) AF: 0.713 AC: 29357 AN: 41182

American (AMR) AF: 0.719 AC: 10945 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2596 AN: 3464

East Asian (EAS) AF: 0.822 AC: 4227 AN: 5144

South Asian (SAS) AF: 0.760 AC: 3661 AN: 4814

European-Finnish (FIN) AF: 0.759 AC: 7841 AN: 10334

Middle Eastern (MID) AF: 0.682 AC: 199 AN: 292

European-Non Finnish (NFE) AF: 0.719 AC: 48818 AN: 67868

Other (OTH) AF: 0.727 AC: 1533 AN: 2108

Alfa AF: 0.722 Hom.: 154096

Bravo AF: 0.723

Asia WGS AF: 0.794 AC: 2764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.63
DANN	Benign	0.17
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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: rs10956197; hg19: chr8-125712420;