chr8-124564440-G-A

Variant names:

• chr8-124564440-G-A
• rs17299208
• NM_014751.6:c.824+1222C>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.824+1222C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0783 in 152,094 control chromosomes in the GnomAD database, including 632 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 (632 hom., cov: 31)
• Consequence: MTSS1 NM_014751.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169
• Publications: 1 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTSS1	NM_014751.6	MANE Select	c.824+1222C>T		intron	N/A	NP_055566.3
	MTSS1	NM_001282971.2		c.836+1222C>T		intron	N/A	NP_001269900.1
	MTSS1	NM_001363294.2		c.824+1222C>T		intron	N/A	NP_001350223.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTSS1	ENST00000518547.6	TSL:1 MANE Select	c.824+1222C>T		intron	N/A	ENSP00000429064.1
	MTSS1	ENST00000378017.7	TSL:1	c.824+1222C>T		intron	N/A	ENSP00000367256.3
	MTSS1	ENST00000431961.6	TSL:1	c.224+1222C>T		intron	N/A	ENSP00000393606.2

Frequencies

GnomAD3 genomes AF: 0.0784 AC: 11911 AN: 151976 Hom.: 632 Cov.: 31

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.0512

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0604

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0829

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

GnomAD4 genome AF: 0.0783 AC: 11914 AN: 152094 Hom.: 632 Cov.: 31 AF XY: 0.0790 AC XY: 5879 AN XY: 74376

African (AFR) AF: 0.0216 AC: 895 AN: 41484

American (AMR) AF: 0.0511 AC: 781 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 357 AN: 3468

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5178

South Asian (SAS) AF: 0.0604 AC: 291 AN: 4814

European-Finnish (FIN) AF: 0.144 AC: 1517 AN: 10560

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

European-Non Finnish (NFE) AF: 0.113 AC: 7713 AN: 67990

Other (OTH) AF: 0.0820 AC: 173 AN: 2110

Alfa AF: 0.106 Hom.: 252

Bravo AF: 0.0696

Asia WGS AF: 0.0310 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.8
DANN	Benign	0.80
PhyloP100		0.17
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: rs17299208; hg19: chr8-125576681;