rs915230

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNM1P17		n.30357169T>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNM1P17	ENST00000512082.1	n.230T>C		non_coding_transcript_exon_variant	Exon 3 of 3	6
MTPAP	ENST00000488290.5	n.1912+7537A>G		intron_variant	Intron 9 of 16	2

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 v4.3

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;