NM_001024593.2:c.378-123C>G

Variant names:

• chr10-73426854-G-C
• rs2297452
• NM_001024593.2:c.378-123C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001024593.2. 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
	MSS51	NM_001024593.2	MANE Select	c.378-123C>G		intron	N/A	NP_001019764.1	Q4VC12-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSS51	ENST00000299432.7	TSL:1 MANE Select	c.378-123C>G		intron	N/A	ENSP00000299432.2	Q4VC12-1
	MSS51	ENST00000372912.1	TSL:1	c.378-123C>G		intron	N/A	ENSP00000362003.1	Q4VC12-1
	MSS51	ENST00000487126.5	TSL:2	n.378-123C>G		intron	N/A	ENSP00000435203.1	F6VAV3

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

African (AFR) AF: 0.458 AC: 10558 AN: 23040

American (AMR) AF: 0.102 AC: 2791 AN: 27262

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 2284 AN: 17894

East Asian (EAS) AF: 0.285 AC: 10403 AN: 36438

South Asian (SAS) AF: 0.221 AC: 13670 AN: 61784

European-Finnish (FIN) AF: 0.0511 AC: 1822 AN: 35658

Middle Eastern (MID) AF: 0.0890 AC: 294 AN: 3304

European-Non Finnish (NFE) AF: 0.0657 AC: 48151 AN: 732492

Other (OTH) AF: 0.117 AC: 5130 AN: 43976

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

African (AFR) AF: 0.447 AC: 18509 AN: 41408

American (AMR) AF: 0.114 AC: 1745 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 455 AN: 3472

East Asian (EAS) AF: 0.300 AC: 1556 AN: 5184

South Asian (SAS) AF: 0.226 AC: 1087 AN: 4820

European-Finnish (FIN) AF: 0.0449 AC: 476 AN: 10608

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0654 AC: 4446 AN: 68014

Other (OTH) AF: 0.148 AC: 311 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.59
PhyloP100		-1.6
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: rs2297452; hg19: chr10-75186612; COSMIC: COSV55020761; COSMIC: COSV55020761;