17-75040148-C-T

Variant names:

• chr17-75040148-C-T
• NM_006356.3:c.235G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006356.3(ATP5PD):​c.235G>A​(p.Val79Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ATP5PD NM_006356.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.542

Genes affected

ATP5PD (HGNC:845): (ATP synthase peripheral stalk subunit d) Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. It is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, which comprises the proton channel. The F1 complex consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled in a ratio of 3 alpha, 3 beta, and a single representative of the other 3. The Fo seems to have nine subunits (a, b, c, d, e, f, g, F6 and 8). This gene encodes the d subunit of the Fo complex. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. In addition, three pseudogenes are located on chromosomes 9, 12 and 15. [provided by RefSeq, Jun 2010]

KCTD2 (HGNC:21294): (potassium channel tetramerization domain containing 2) Predicted to enable cullin family protein binding activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Predicted to be part of Cul3-RING ubiquitin ligase complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.084958404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP5PD	NM_006356.3	c.235G>A	p.Val79Ile	missense_variant	Exon 4 of 6	ENST00000301587.9	NP_006347.1
ATP5PD	NM_001003785.2	c.220-877G>A		intron_variant	Intron 3 of 4		NP_001003785.1
KCTD2	NR_110835.2	n.365+4791C>T		intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP5PD	ENST00000301587.9	c.235G>A	p.Val79Ile	missense_variant	Exon 4 of 6	1	NM_006356.3	ENSP00000301587.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459652 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726148

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.075
DANN	Benign	0.89
DEOGEN2	Benign	0.084	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.0050	N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.13	N
REVEL	Benign	0.041
Sift	Benign	0.83	T
Sift4G	Benign	0.45	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.56		Loss of ubiquitination at K78 (P = 0.0533);
MVP		0.15
MPC		0.18
ClinPred		0.033	T
GERP RS		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.011
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-73036243;