rs7911488

Positions:

• chr10-103394332-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032747.4(ATP5MK):​c.-143T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 533,164 control chromosomes in the GnomAD database, including 32,579 homozygotes. 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: 𝑓 0.27 (6595 hom., cov: 32)
  • Exomes 𝑓: 0.36 (25984 hom.)
• Consequence: ATP5MK NM_032747.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

Genes affected

ATP5MK (HGNC:30889): (ATP synthase membrane subunit k) Located in mitochondrion. Part of mitochondrial proton-transporting ATP synthase complex. Implicated in mitochondrial complex V (ATP synthase) deficiency nuclear type 6. [provided by Alliance of Genome Resources, Apr 2022]

MIR1307 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP5MK	NM_001206427.2	c.-10+1414T>C		intron_variant		ENST00000369815.6	NP_001193356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP5MK	ENST00000369815.6	c.-10+1414T>C		intron_variant		2	NM_001206427.2	ENSP00000358830.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40989 AN: 151960 Hom.: 6591 Cov.: 32

Gnomad AFR AF: 0.0924

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.277

GnomAD3 exomes AF: 0.340 AC: 84712 AN: 249002 Hom.: 15534 AF XY: 0.353 AC XY: 47787 AN XY: 135320

Gnomad AFR exome AF: 0.0866

Gnomad AMR exome AF: 0.307

Gnomad ASJ exome AF: 0.310

Gnomad EAS exome AF: 0.344

Gnomad SAS exome AF: 0.508

Gnomad FIN exome AF: 0.399

Gnomad NFE exome AF: 0.331

Gnomad OTH exome AF: 0.337

GnomAD4 exome AF: 0.357 AC: 136113 AN: 381088 Hom.: 25984 Cov.: 0 AF XY: 0.371 AC XY: 80428 AN XY: 216808

Gnomad4 AFR exome AF: 0.0890

Gnomad4 AMR exome AF: 0.308

Gnomad4 ASJ exome AF: 0.312

Gnomad4 EAS exome AF: 0.338

Gnomad4 SAS exome AF: 0.508

Gnomad4 FIN exome AF: 0.397

Gnomad4 NFE exome AF: 0.330

Gnomad4 OTH exome AF: 0.324

GnomAD4 genome AF: 0.270 AC: 40995 AN: 152076 Hom.: 6595 Cov.: 32 AF XY: 0.276 AC XY: 20536 AN XY: 74298

Gnomad4 AFR AF: 0.0922

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.277

Alfa AF: 0.313 Hom.: 10178

Bravo AF: 0.250

Asia WGS AF: 0.392 AC: 1361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7911488; hg19: chr10-105154089; COSMIC: COSV58915207; COSMIC: COSV58915207;