chr8-124606962-T-C

Variant names:

• chr8-124606962-T-C
• rs2013845
• NM_014751.6:c.209-15727A>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.209-15727A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 151,972 control chromosomes in the GnomAD database, including 7,818 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 0.29 (7818 hom., cov: 31)
• Consequence: MTSS1 NM_014751.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 4 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]

LOC124902016 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014751.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTSS1	NM_014751.6	MANE Select	c.209-15727A>G		intron	N/A	NP_055566.3
	MTSS1	NM_001282971.2		c.209-15727A>G		intron	N/A	NP_001269900.1	O43312-5
	MTSS1	NM_001363294.2		c.209-15727A>G		intron	N/A	NP_001350223.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTSS1	ENST00000518547.6	TSL:1 MANE Select	c.209-15727A>G		intron	N/A	ENSP00000429064.1	O43312-1
	MTSS1	ENST00000378017.7	TSL:1	c.209-15727A>G		intron	N/A	ENSP00000367256.3	O43312-4
	MTSS1	ENST00000325064.9	TSL:2	c.209-15727A>G		intron	N/A	ENSP00000322804.5	O43312-5

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43877 AN: 151854 Hom.: 7794 Cov.: 31

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.289 AC: 43945 AN: 151972 Hom.: 7818 Cov.: 31 AF XY: 0.291 AC XY: 21650 AN XY: 74298

African (AFR) AF: 0.492 AC: 20382 AN: 41388

American (AMR) AF: 0.288 AC: 4397 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 466 AN: 3468

East Asian (EAS) AF: 0.326 AC: 1681 AN: 5158

South Asian (SAS) AF: 0.252 AC: 1212 AN: 4818

European-Finnish (FIN) AF: 0.236 AC: 2498 AN: 10586

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12391 AN: 67966

Other (OTH) AF: 0.274 AC: 577 AN: 2104

Alfa AF: 0.217 Hom.: 13569

Bravo AF: 0.306

Asia WGS AF: 0.347 AC: 1205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.26
DANN	Benign	0.45
PhyloP100		-1.4
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: rs2013845; hg19: chr8-125619203;