rs2074513

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-1242049-C-A
• chr19-1242049-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001687.5(ATP5F1D):​c.141+58C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000017 in 1,176,888 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: ATP5F1D NM_001687.5 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP5F1D	NM_001687.5	c.141+58C>A		intron_variant	Intron 1 of 3	ENST00000215375.7	NP_001678.1
ATP5F1D	NM_001001975.2	c.141+58C>A		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>A		intron_variant	Intron 1 of 3	1	NM_001687.5	ENSP00000215375.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000170 AC: 2 AN: 1176888 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 568814

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24506

American (AMR) AF: 0.00 AC: 0 AN: 16476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15400

East Asian (EAS) AF: 0.00 AC: 0 AN: 29722

South Asian (SAS) AF: 0.0000245 AC: 1 AN: 40778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27700

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3872

European-Non Finnish (NFE) AF: 0.00000103 AC: 1 AN: 971258

Other (OTH) AF: 0.00 AC: 0 AN: 47176

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.038550), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	3.7
DANN	Benign	0.96
PhyloP100		-0.041
PromoterAI		-0.17	Neutral

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;