chr1-151760903-CAA-C

Position:

• chr1-151760903-CAA-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_031420.4(MRPL9):​c.589-6_589-5del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0426 in 919,182 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 0)
  • Exomes 𝑓: 0.046 (0 hom.)
• Consequence: MRPL9 NM_031420.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93

Genes affected

MRPL9 (HGNC:14277): (mitochondrial ribosomal protein L9) This is a nuclear gene encoding a protein component of the 39S subunit of the mitochondrial ribosome. Alternative splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 8. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL9	NM_031420.4	c.589-6_589-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000368830.8
MRPL9	NM_001300733.2	c.487-6_487-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
MRPL9	NR_125331.2	n.646-6_646-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL9	ENST00000368830.8	c.589-6_589-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_031420.4	P1

Frequencies

GnomAD3 genomes AF: 0.000270 AC: 20 AN: 74192 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000111

Gnomad AMI AF: 0.00183

Gnomad AMR AF: 0.000153

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00250

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000282

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0463 AC: 39101 AN: 844996 Hom.: 0 AF XY: 0.0466 AC XY: 19542 AN XY: 419144

Gnomad4 AFR exome AF: 0.0309

Gnomad4 AMR exome AF: 0.0430

Gnomad4 ASJ exome AF: 0.0369

Gnomad4 EAS exome AF: 0.0419

Gnomad4 SAS exome AF: 0.0587

Gnomad4 FIN exome AF: 0.0349

Gnomad4 NFE exome AF: 0.0468

Gnomad4 OTH exome AF: 0.0457

GnomAD4 genome AF: 0.000270 AC: 20 AN: 74186 Hom.: 0 Cov.: 0 AF XY: 0.000353 AC XY: 12 AN XY: 33956

Gnomad4 AFR AF: 0.000111

Gnomad4 AMR AF: 0.000153

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00250

Gnomad4 NFE AF: 0.000282

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs755031728; hg19: chr1-151733379;