8-124558488-T-A

Variant names:

• chr8-124558488-T-A
• rs7830235
• NM_014751.6:c.1036-613A>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.1036-613A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.078 in 152,136 control chromosomes in the GnomAD database, including 622 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 0.078 (622 hom., cov: 31)
• Consequence: MTSS1 NM_014751.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.898
• 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]

NDUFB9 (HGNC:7704): (NADH:ubiquinone oxidoreductase subunit B9) The protein encoded by this gene is a subunit of the mitochondrial oxidative phosphorylation complex I (nicotinamide adenine dinucleotide: ubiquinone oxidoreductase). Complex I is localized to the inner mitochondrial membrane and functions to dehydrogenate nicotinamide adenine dinucleotide and to shuttle electrons to coenzyme Q. Complex I deficiency is the most common defect found in oxidative phosphorylation disorders and results in a range of conditions, including lethal neonatal disease, hypertrophic cardiomyopathy, liver disease, and adult-onset neurodegenerative disorders. Pseudogenes of this gene are found on chromosomes five, seven and eight. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

NDUFB9 Gene-Disease associations (from GenCC):

• mitochondrial complex I deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• mitochondrial complex I deficiency, nuclear type 24

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTSS1	NM_014751.6	c.1036-613A>T		intron_variant	Intron 10 of 13	ENST00000518547.6	NP_055566.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTSS1	ENST00000518547.6	c.1036-613A>T		intron_variant	Intron 10 of 13	1	NM_014751.6	ENSP00000429064.1

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11868 AN: 152018 Hom.: 622 Cov.: 31

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.0510

Gnomad ASJ AF: 0.0982

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0616

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0833

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

GnomAD4 genome AF: 0.0780 AC: 11872 AN: 152136 Hom.: 622 Cov.: 31 AF XY: 0.0788 AC XY: 5861 AN XY: 74364

African (AFR) AF: 0.0214 AC: 889 AN: 41550

American (AMR) AF: 0.0509 AC: 779 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0982 AC: 341 AN: 3472

East Asian (EAS) AF: 0.00194 AC: 10 AN: 5166

South Asian (SAS) AF: 0.0619 AC: 298 AN: 4818

European-Finnish (FIN) AF: 0.142 AC: 1495 AN: 10564

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7710 AN: 67964

Other (OTH) AF: 0.0825 AC: 174 AN: 2110

Alfa AF: 0.0484 Hom.: 44

Bravo AF: 0.0694

Asia WGS AF: 0.0320 AC: 111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	3.3
DANN	Benign	0.88
PhyloP100		-0.90
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: rs7830235; hg19: chr8-125570729;