rs2297452

chr10-73426854-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001024593.2(MSS51):c.378-123C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,133,956 control chromosomes in the GnomAD database, including 12,884 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 0.19 (4966 hom., cov: 32)
  • Exomes 𝑓: 0.097 (7918 hom.)
• Consequence: MSS51 NM_001024593.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

Genes affected

MSS51 (HGNC:21000): (MSS51 mitochondrial translational activator) Predicted to enable metal ion binding activity. [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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSS51	NM_001024593.2	c.378-123C>G		intron_variant		ENST00000299432.7
MSS51	XM_047424550.1	c.378-123C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSS51	ENST00000299432.7	c.378-123C>G		intron_variant		1	NM_001024593.2	P1
MSS51	ENST00000372912.1	c.378-123C>G		intron_variant		1		P1
MSS51	ENST00000487126.5	c.378-123C>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28631 AN: 151990 Hom.: 4940 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.0449

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0653

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.0969 AC: 95103 AN: 981848 Hom.: 7918 AF XY: 0.0997 AC XY: 49337 AN XY: 494744

Gnomad4 AFR exome AF: 0.458

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.128

Gnomad4 EAS exome AF: 0.285

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.0511

Gnomad4 NFE exome AF: 0.0657

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.189 AC: 28713 AN: 152108 Hom.: 4966 Cov.: 32 AF XY: 0.189 AC XY: 14035 AN XY: 74388

Gnomad4 AFR AF: 0.447

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.0449

Gnomad4 NFE AF: 0.0654

Gnomad4 OTH AF: 0.148

Alfa AF: 0.138 Hom.: 395

Bravo AF: 0.203

Asia WGS AF: 0.270 AC: 939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.2
Dann	Benign	0.59

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: rs2297452; hg19: chr10-75186612; COSMIC: COSV55020761; COSMIC: COSV55020761;