chr8-124709125-G-A

Position:

• chr8-124709125-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014751.6(MTSS1):​c.73-4934C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0304 in 152,194 control chromosomes in the GnomAD database, including 117 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 0.030 (117 hom., cov: 32)
• Consequence: MTSS1 NM_014751.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114

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=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0304 (4627/152194) while in subpopulation NFE AF= 0.0437 (2974/68010). AF 95% confidence interval is 0.0424. There are 117 homozygotes in gnomad4. There are 2341 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4627 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTSS1	NM_014751.6	c.73-4934C>T		intron_variant		ENST00000518547.6	NP_055566.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTSS1	ENST00000518547.6	c.73-4934C>T		intron_variant		1	NM_014751.6	ENSP00000429064	P4

Frequencies

GnomAD3 genomes AF: 0.0304 AC: 4626 AN: 152076 Hom.: 117 Cov.: 32

Gnomad AFR AF: 0.00790

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00725

Gnomad FIN AF: 0.0837

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0437

Gnomad OTH AF: 0.0249

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

GnomAD4 genome AF: 0.0304 AC: 4627 AN: 152194 Hom.: 117 Cov.: 32 AF XY: 0.0315 AC XY: 2341 AN XY: 74394

Gnomad4 AFR AF: 0.00790

Gnomad4 AMR AF: 0.0176

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00747

Gnomad4 FIN AF: 0.0837

Gnomad4 NFE AF: 0.0437

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0353 Hom.: 12

Bravo AF: 0.0250

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.58

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: rs11781525; hg19: chr8-125721366;