8-120443315-G-A

Position:

• chr8-120443315-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000306185.8(MRPL13):​c.28-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,469,226 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (12 hom., cov: 28)
  • Exomes 𝑓: 0.00094 (2 hom.)
• Consequence: MRPL13 ENST00000306185.8 splice_region, intron
• Scores: Splicing: ADA: 0.00005542
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.02

Genes affected

MRPL13 (HGNC:14278): (mitochondrial ribosomal protein L13) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. [provided by RefSeq, Jul 2008]

MRPL13 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 8-120443315-G-A is Benign according to our data. Variant chr8-120443315-G-A is described in ClinVar as [Benign]. Clinvar id is 787333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0188 (1237/65652) while in subpopulation AFR AF= 0.0383 (1118/29176). AF 95% confidence interval is 0.0365. There are 12 homozygotes in gnomad4. There are 607 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL13	NM_014078.6	c.28-7C>T		splice_region_variant, intron_variant		ENST00000306185.8	NP_054797.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL13	ENST00000306185.8	c.28-7C>T		splice_region_variant, intron_variant		1	NM_014078.6	ENSP00000306548.3
MRPL13	ENST00000518696.5	n.28-7C>T		splice_region_variant, intron_variant		1		ENSP00000428867.1
MRPL13	ENST00000518918.1	c.-45-7C>T		splice_region_variant, intron_variant		2		ENSP00000430545.1
MRPL13	ENST00000520677.1	n.33-7C>T		splice_region_variant, intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 1231 AN: 65552 Hom.: 11 Cov.: 28

Gnomad AFR AF: 0.0382

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0224

Gnomad NFE AF: 0.00119

Gnomad OTH AF: 0.0205

GnomAD3 exomes AF: 0.00305 AC: 428 AN: 140418 Hom.: 0 AF XY: 0.00237 AC XY: 183 AN XY: 77188

Gnomad AFR exome AF: 0.0298

Gnomad AMR exome AF: 0.00263

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000134

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000449

Gnomad OTH exome AF: 0.00254

GnomAD4 exome AF: 0.000937 AC: 1315 AN: 1403574 Hom.: 2 Cov.: 30 AF XY: 0.000859 AC XY: 599 AN XY: 697244

Gnomad4 AFR exome AF: 0.0255

Gnomad4 AMR exome AF: 0.00207

Gnomad4 ASJ exome AF: 0.0000427

Gnomad4 EAS exome AF: 0.0000259

Gnomad4 SAS exome AF: 0.000143

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000318

Gnomad4 OTH exome AF: 0.00179

GnomAD4 genome AF: 0.0188 AC: 1237 AN: 65652 Hom.: 12 Cov.: 28 AF XY: 0.0186 AC XY: 607 AN XY: 32564

Gnomad4 AFR AF: 0.0383

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00119

Gnomad4 OTH AF: 0.0204

Alfa AF: 0.00405 Hom.: 1

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 18, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.97
DANN	Benign	0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000055
dbscSNV1_RF	Benign	0.0040
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: rs201756990; hg19: chr8-121455555;