rs575276701

Variant names:

• chr2-27309499-T-A
• rs575276701
• NM_002437.5:c.*413A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-27309499-T-A
• chr2-27309499-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002437.5(MPV17):​c.*413A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000175 in 286,296 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000074 (0 hom.)
• Consequence: MPV17 NM_002437.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192
• Publications: 0 publications found

Genes affected

MPV17 (HGNC:7224): (mitochondrial inner membrane protein MPV17) This gene encodes a mitochondrial inner membrane protein that is implicated in the metabolism of reactive oxygen species. Mutations in this gene have been associated with the hepatocerebral form of mitochondrial DNA depletion syndrome (MDDS). [provided by RefSeq, Jul 2008]

TRIM54 (HGNC:16008): (tripartite motif containing 54) The protein encoded by this gene contains a RING finger motif and is highly similar to the ring finger proteins RNF28/MURF1 and RNF29/MURF2. In vitro studies demonstrated that this protein, RNF28, and RNF29 form heterodimers, which may be important for the regulation of titin kinase and microtubule-dependent signal pathways in striated muscles. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002437.5. 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
	MPV17	NM_002437.5	MANE Select	c.*413A>T		3_prime_UTR	Exon 8 of 8	NP_002428.1	P39210

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPV17	ENST00000380044.6	TSL:1 MANE Select	c.*413A>T		3_prime_UTR	Exon 8 of 8	ENSP00000369383.1	P39210
	MPV17	ENST00000233545.6	TSL:1	c.*413A>T		3_prime_UTR	Exon 7 of 7	ENSP00000233545.2	P39210
	MPV17	ENST00000911060.1		c.*413A>T		3_prime_UTR	Exon 10 of 10	ENSP00000581119.1

Frequencies

GnomAD3 genomes AF: 0.0000264 AC: 4 AN: 151694 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000970

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000743 AC: 1 AN: 134602 Hom.: 0 Cov.: 0 AF XY: 0.0000146 AC XY: 1 AN XY: 68620

African (AFR) AF: 0.000182 AC: 1 AN: 5502

American (AMR) AF: 0.00 AC: 0 AN: 6126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4998

East Asian (EAS) AF: 0.00 AC: 0 AN: 10834

South Asian (SAS) AF: 0.00 AC: 0 AN: 7826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 624

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 84264

Other (OTH) AF: 0.00 AC: 0 AN: 8252

GnomAD4 genome AF: 0.0000264 AC: 4 AN: 151694 Hom.: 0 Cov.: 32 AF XY: 0.0000405 AC XY: 3 AN XY: 74080

African (AFR) AF: 0.0000970 AC: 4 AN: 41234

American (AMR) AF: 0.00 AC: 0 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.2
DANN	Benign	0.76
PhyloP100		0.19

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: rs575276701; hg19: chr2-27532367;