rs7911488

Variant names:

• chr10-103394332-A-G
• rs7911488
• ENST00000337003.4:c.-143T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000337003.4(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 ENST00000337003.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 76 publications found

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:35372): (microRNA 1307) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ATP5MK	NM_001206427.2	c.-10+1414T>C		intron_variant	Intron 2 of 4	ENST00000369815.6	NP_001193356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP5MK	ENST00000369815.6	c.-10+1414T>C		intron_variant	Intron 2 of 4	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

GnomAD2 exomes AF: 0.340 AC: 84712 AN: 249002 AF XY: 0.353

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 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

African (AFR) AF: 0.0890 AC: 934 AN: 10496

American (AMR) AF: 0.308 AC: 11187 AN: 36282

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 3663 AN: 11722

East Asian (EAS) AF: 0.338 AC: 4440 AN: 13134

South Asian (SAS) AF: 0.508 AC: 33856 AN: 66658

European-Finnish (FIN) AF: 0.397 AC: 12824 AN: 32298

Middle Eastern (MID) AF: 0.300 AC: 854 AN: 2850

European-Non Finnish (NFE) AF: 0.330 AC: 62958 AN: 190986

Other (OTH) AF: 0.324 AC: 5397 AN: 16662

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

African (AFR) AF: 0.0922 AC: 3827 AN: 41524

American (AMR) AF: 0.296 AC: 4513 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1064 AN: 3468

East Asian (EAS) AF: 0.350 AC: 1809 AN: 5166

South Asian (SAS) AF: 0.503 AC: 2420 AN: 4814

European-Finnish (FIN) AF: 0.400 AC: 4211 AN: 10540

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22271 AN: 67982

Other (OTH) AF: 0.277 AC: 584 AN: 2112

Alfa AF: 0.304 Hom.: 24546

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
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7911488; hg19: chr10-105154089; COSMIC: COSV58915207; COSMIC: COSV58915207;