rs6989466

Variant names:

• chr8-124617619-A-C
• rs6989466
• NM_014751.6:c.209-26384T>G

Variant summary

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

The NM_014751.6(MTSS1):​c.209-26384T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,880 control chromosomes in the GnomAD database, including 10,280 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 0.31 (10280 hom., cov: 31)
• Consequence: MTSS1 NM_014751.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTSS1	NM_014751.6	c.209-26384T>G		intron_variant	Intron 3 of 13	ENST00000518547.6	NP_055566.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTSS1	ENST00000518547.6	c.209-26384T>G		intron_variant	Intron 3 of 13	1	NM_014751.6	ENSP00000429064.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47523 AN: 151760 Hom.: 10232 Cov.: 31

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.314 AC: 47630 AN: 151880 Hom.: 10280 Cov.: 31 AF XY: 0.315 AC XY: 23412 AN XY: 74208

African (AFR) AF: 0.607 AC: 25119 AN: 41394

American (AMR) AF: 0.303 AC: 4627 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 424 AN: 3466

East Asian (EAS) AF: 0.322 AC: 1660 AN: 5160

South Asian (SAS) AF: 0.253 AC: 1216 AN: 4798

European-Finnish (FIN) AF: 0.216 AC: 2280 AN: 10548

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11383 AN: 67930

Other (OTH) AF: 0.280 AC: 592 AN: 2114

Alfa AF: 0.223 Hom.: 2385

Bravo AF: 0.336

Asia WGS AF: 0.357 AC: 1241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.39
PhyloP100		-0.21
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: rs6989466; hg19: chr8-125629860;