chr19-1242049-C-T

Variant names:

• chr19-1242049-C-T
• rs2074513
• NM_001687.5:c.141+58C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001687.5(ATP5F1D):​c.141+58C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,328,594 control chromosomes in the GnomAD database, including 24,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2165 hom., cov: 32)
  • Exomes 𝑓: 0.19 (22831 hom.)
• Consequence: ATP5F1D NM_001687.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0410

Genes affected

ATP5F1D (HGNC:837): (ATP synthase F1 subunit delta) This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. ATP synthase is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and a single representative of the other 3. The proton channel consists of three main subunits (a, b, c). This gene encodes the delta subunit of the catalytic core. Alternatively spliced transcript variants encoding the same isoform have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 19-1242049-C-T is Benign according to our data. Variant chr19-1242049-C-T is described in ClinVar as [Benign]. Clinvar id is 1175553.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP5F1D	NM_001687.5	c.141+58C>T		intron_variant	Intron 1 of 3	ENST00000215375.7	NP_001678.1
ATP5F1D	NM_001001975.2	c.141+58C>T		intron_variant	Intron 1 of 4		NP_001001975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP5F1D	ENST00000215375.7	c.141+58C>T		intron_variant	Intron 1 of 3	1	NM_001687.5	ENSP00000215375.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23182 AN: 151892 Hom.: 2168 Cov.: 32

Gnomad AFR AF: 0.0643

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.194 AC: 228764 AN: 1176596 Hom.: 22831 Cov.: 31 AF XY: 0.195 AC XY: 110629 AN XY: 568660

African (AFR) AF: 0.0632 AC: 1550 AN: 24506

American (AMR) AF: 0.142 AC: 2343 AN: 16466

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 2252 AN: 15400

East Asian (EAS) AF: 0.314 AC: 9329 AN: 29702

South Asian (SAS) AF: 0.182 AC: 7414 AN: 40746

European-Finnish (FIN) AF: 0.203 AC: 5612 AN: 27676

Middle Eastern (MID) AF: 0.130 AC: 504 AN: 3872

European-Non Finnish (NFE) AF: 0.197 AC: 191070 AN: 971060

Other (OTH) AF: 0.184 AC: 8690 AN: 47168

GnomAD4 genome AF: 0.153 AC: 23185 AN: 151998 Hom.: 2165 Cov.: 32 AF XY: 0.155 AC XY: 11477 AN XY: 74278

African (AFR) AF: 0.0643 AC: 2667 AN: 41500

American (AMR) AF: 0.148 AC: 2271 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 509 AN: 3472

East Asian (EAS) AF: 0.326 AC: 1668 AN: 5118

South Asian (SAS) AF: 0.183 AC: 880 AN: 4814

European-Finnish (FIN) AF: 0.192 AC: 2029 AN: 10584

Middle Eastern (MID) AF: 0.127 AC: 37 AN: 292

European-Non Finnish (NFE) AF: 0.187 AC: 12730 AN: 67908

Other (OTH) AF: 0.150 AC: 316 AN: 2104

Alfa AF: 0.163 Hom.: 292

Bravo AF: 0.145

Asia WGS AF: 0.219 AC: 756 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 10, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.6
DANN	Uncertain	0.98
PhyloP100		-0.041
PromoterAI		-0.10	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Publications

LitVar

Other links and lift over

dbSNP: rs2074513; hg19: chr19-1242048; COSMIC: COSV53066538; COSMIC: COSV53066538;