rs139217290

chr10-30341649-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_018109.4(MTPAP):c.158-9C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000915 in 1,613,574 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00053 (6 hom.)
• Consequence: MTPAP NM_018109.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002277
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.34

Genes affected

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 10-30341649-G-A is Benign according to our data. Variant chr10-30341649-G-A is described in ClinVar as [Benign]. Clinvar id is 378178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-30341649-G-A is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTPAP	NM_018109.4	c.158-9C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000263063.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTPAP	ENST00000263063.9	c.158-9C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_018109.4	P1
MTPAP	ENST00000417581.1	c.-38-9C>T		splice_polypyrimidine_tract_variant, intron_variant		5
MTPAP	ENST00000421701.1	c.44-9C>T		splice_polypyrimidine_tract_variant, intron_variant		2
MTPAP	ENST00000488290.5	n.1913-9C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00462 AC: 703 AN: 152124 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00141 AC: 355 AN: 250892 Hom.: 3 AF XY: 0.00118 AC XY: 160 AN XY: 135646

Gnomad AFR exome AF: 0.0159

Gnomad AMR exome AF: 0.000520

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00250

Gnomad SAS exome AF: 0.000849

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.000979

GnomAD4 exome AF: 0.000528 AC: 772 AN: 1461332 Hom.: 6 Cov.: 31 AF XY: 0.000506 AC XY: 368 AN XY: 726984

Gnomad4 AFR exome AF: 0.0157

Gnomad4 AMR exome AF: 0.000872

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00156

Gnomad4 SAS exome AF: 0.000881

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.000994

GnomAD4 genome AF: 0.00462 AC: 704 AN: 152242 Hom.: 1 Cov.: 32 AF XY: 0.00458 AC XY: 341 AN XY: 74434

Gnomad4 AFR AF: 0.0149

Gnomad4 AMR AF: 0.00347

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00222 Hom.: 2

Bravo AF: 0.00534

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Feb 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 09, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:2

Likely benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Sep 18, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 26, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	14
Dann	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000023
dbscSNV1_RF	Benign	0.082
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: rs139217290; hg19: chr10-30630578;