chr7-99419979-A-G

Variant names:

• chr7-99419979-A-G
• rs146460719
• NM_015545.4:c.2091T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_015545.4(PTCD1):​c.2091T>C​(p.Leu697Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00652 in 1,614,212 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0052 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0067 (47 hom.)
• Consequence: PTCD1 NM_015545.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.231
• Publications: 1 publications found

Genes affected

PTCD1 (HGNC:22198): (pentatricopeptide repeat domain 1) This gene encodes a mitochondrial protein that binds leucine tRNAs and other mitochondrial RNAs and plays a role in the regulation of translation. Increased expression of this gene results in decreased mitochondrial leucine tRNA levels. Naturally occurring read-through transcription exists between upstream ATP5J2 (ATP synthase, H+ transporting, mitochondrial Fo complex, subunit F2) and this gene. [provided by RefSeq, Aug 2015]

ATP5MF-PTCD1 (HGNC:38844): (ATP5MF-PTCD1 readthrough) This locus represents naturally occurring read-through transcription between the ATP5J2 (ATP synthase, H+ transporting, mitochondrial Fo complex, subunit F2) and PTCD1 (pentatricopeptide repeat domain 1) genes on chromosome 7. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 7-99419979-A-G is Benign according to our data. Variant chr7-99419979-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2657720.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.231 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015545.4. 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
	PTCD1	NM_015545.4	MANE Select	c.2091T>C	p.Leu697Leu	synonymous	Exon 8 of 8	NP_056360.2
	ATP5MF-PTCD1	NM_001198879.2		c.2238T>C	p.Leu746Leu	synonymous	Exon 9 of 9	NP_001185808.1	G3V325

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTCD1	ENST00000292478.9	TSL:1 MANE Select	c.2091T>C	p.Leu697Leu	synonymous	Exon 8 of 8	ENSP00000292478.5	O75127
	ATP5MF-PTCD1	ENST00000413834.5	TSL:2	c.2238T>C	p.Leu746Leu	synonymous	Exon 9 of 9	ENSP00000400168.1	G3V325
	PTCD1	ENST00000910801.1		c.2091T>C	p.Leu697Leu	synonymous	Exon 8 of 8	ENSP00000580860.1

Frequencies

GnomAD3 genomes AF: 0.00522 AC: 794 AN: 152212 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.0104

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00767

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00643 AC: 1617 AN: 251460 AF XY: 0.00675

Gnomad AFR exome AF: 0.00172

Gnomad AMR exome AF: 0.00266

Gnomad ASJ exome AF: 0.00516

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0104

Gnomad NFE exome AF: 0.00899

Gnomad OTH exome AF: 0.00684

GnomAD4 exome AF: 0.00665 AC: 9724 AN: 1461882 Hom.: 47 Cov.: 31 AF XY: 0.00675 AC XY: 4906 AN XY: 727246

African (AFR) AF: 0.00111 AC: 37 AN: 33480

American (AMR) AF: 0.00280 AC: 125 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00417 AC: 109 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00454 AC: 392 AN: 86258

European-Finnish (FIN) AF: 0.0121 AC: 646 AN: 53416

Middle Eastern (MID) AF: 0.00711 AC: 41 AN: 5766

European-Non Finnish (NFE) AF: 0.00723 AC: 8041 AN: 1112010

Other (OTH) AF: 0.00551 AC: 333 AN: 60396

GnomAD4 genome AF: 0.00521 AC: 794 AN: 152330 Hom.: 2 Cov.: 32 AF XY: 0.00529 AC XY: 394 AN XY: 74488

African (AFR) AF: 0.00101 AC: 42 AN: 41574

American (AMR) AF: 0.00274 AC: 42 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00393 AC: 19 AN: 4832

European-Finnish (FIN) AF: 0.0104 AC: 111 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00767 AC: 522 AN: 68018

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00669 Hom.: 4

Bravo AF: 0.00476

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00867

EpiControl AF: 0.00913

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.38
DANN	Benign	0.64
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism

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: rs146460719; hg19: chr7-99017602;