1-151760903-CAAAAAAAAAAAA-CAAAAAAAAA

Variant names:

• chr1-151760903-CAAA-C
• rs755031728
• NM_031420.4:c.589-7_589-5delTTT

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP6 BS1

The NM_031420.4(MRPL9):​c.589-7_589-5delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00922 in 939,378 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 0)
  • Exomes 𝑓: 0.010 (0 hom.)
• Consequence: MRPL9 NM_031420.4 splice_region, 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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 1-151760903-CAAA-C is Benign according to our data. Variant chr1-151760903-CAAA-C is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.01 (8651/865188) while in subpopulation SAS AF= 0.0161 (684/42420). AF 95% confidence interval is 0.0151. There are 0 homozygotes in gnomad4_exome. There are 4364 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL9	NM_031420.4	c.589-7_589-5delTTT		splice_region_variant, intron_variant	Intron 5 of 6	ENST00000368830.8	NP_113608.1
MRPL9	NM_001300733.2	c.487-7_487-5delTTT		splice_region_variant, intron_variant	Intron 4 of 5		NP_001287662.1
MRPL9	NR_125331.2	n.646-7_646-5delTTT		splice_region_variant, intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL9	ENST00000368830.8	c.589-7_589-5delTTT		splice_region_variant, intron_variant	Intron 5 of 6	1	NM_031420.4	ENSP00000357823.3

Frequencies

GnomAD3 genomes AF: 0.000162 AC: 12 AN: 74196 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000153

Gnomad ASJ AF: 0.00136

Gnomad EAS AF: 0.000377

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000499

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000512

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0100 AC: 8651 AN: 865188 Hom.: 0 AF XY: 0.0102 AC XY: 4364 AN XY: 429496

Gnomad4 AFR exome AF: 0.00763

Gnomad4 AMR exome AF: 0.0118

Gnomad4 ASJ exome AF: 0.00722

Gnomad4 EAS exome AF: 0.00761

Gnomad4 SAS exome AF: 0.0161

Gnomad4 FIN exome AF: 0.00717

Gnomad4 NFE exome AF: 0.00989

Gnomad4 OTH exome AF: 0.0102

GnomAD4 genome AF: 0.000162 AC: 12 AN: 74190 Hom.: 0 Cov.: 0 AF XY: 0.000206 AC XY: 7 AN XY: 33958

Gnomad4 AFR AF: 0.000221

Gnomad4 AMR AF: 0.000153

Gnomad4 ASJ AF: 0.00136

Gnomad4 EAS AF: 0.000379

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000499

Gnomad4 NFE AF: 0.0000513

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;