chr10-30357169-T-C

Variant names:

• chr10-30357169-T-C
• rs915230
• ENST00000512082.1:n.230T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000512082.1(DNM1P17):​n.230T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 624,258 control chromosomes in the GnomAD database, including 70,316 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 0.41 (15646 hom., cov: 32)
  • Exomes 𝑓: 0.46 (54670 hom.)
• Consequence: DNM1P17 ENST00000512082.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.16
• Publications: 6 publications found

Genes affected

DNM1P17 (HGNC:21134): (dynamin 1 pseudogene 17)

MTPAP (HGNC:25532): (mitochondrial poly(A) polymerase) The protein encoded by this gene is a member of the DNA polymerase type-B-like family. This enzyme synthesizes the 3' poly(A) tail of mitochondrial transcripts and plays a role in replication-dependent histone mRNA degradation.[provided by RefSeq, Jan 2011]

MTPAP Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• spastic ataxia 4

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000512082.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNM1P17	ENST00000512082.1	TSL:6	n.230T>C		non_coding_transcript_exon	Exon 3 of 3
	MTPAP	ENST00000488290.5	TSL:2	n.1912+7537A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62656 AN: 151978 Hom.: 15643 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.457

GnomAD4 exome AF: 0.459 AC: 216814 AN: 472160 Hom.: 54670 Cov.: 0 AF XY: 0.463 AC XY: 120640 AN XY: 260538

African (AFR) AF: 0.108 AC: 1590 AN: 14782

American (AMR) AF: 0.543 AC: 18287 AN: 33660

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 6868 AN: 14162

East Asian (EAS) AF: 0.119 AC: 3375 AN: 28444

South Asian (SAS) AF: 0.429 AC: 26046 AN: 60778

European-Finnish (FIN) AF: 0.457 AC: 16175 AN: 35384

Middle Eastern (MID) AF: 0.530 AC: 1625 AN: 3066

European-Non Finnish (NFE) AF: 0.511 AC: 131700 AN: 257618

Other (OTH) AF: 0.459 AC: 11148 AN: 24266

GnomAD4 genome AF: 0.412 AC: 62660 AN: 152098 Hom.: 15646 Cov.: 32 AF XY: 0.411 AC XY: 30565 AN XY: 74356

African (AFR) AF: 0.130 AC: 5414 AN: 41518

American (AMR) AF: 0.527 AC: 8053 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1909 AN: 3470

East Asian (EAS) AF: 0.176 AC: 913 AN: 5184

South Asian (SAS) AF: 0.428 AC: 2063 AN: 4824

European-Finnish (FIN) AF: 0.488 AC: 5163 AN: 10578

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37615 AN: 67942

Other (OTH) AF: 0.452 AC: 954 AN: 2110

Alfa AF: 0.472 Hom.: 2481

Bravo AF: 0.404

Asia WGS AF: 0.287 AC: 1000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.24
PhyloP100		3.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs915230; hg19: chr10-30646098;