rs10956197

chr8-124700179-G-Achr8-124700179-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MTSS1	NM_014751.6	c.135-580C>T		intron_variant		ENST00000518547.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTSS1	ENST00000518547.6	c.135-580C>T		intron_variant		1	NM_014751.6	P4

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

Gnomad4 AFR AF: 0.713

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.822

Gnomad4 SAS AF: 0.760

Gnomad4 FIN AF: 0.759

Gnomad4 NFE AF: 0.719

Gnomad4 OTH AF: 0.727

Alfa AF: 0.722 Hom.: 66736

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

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: rs10956197; hg19: chr8-125712420;