chr11-1952119-G-A

Variant names:

• chr11-1952119-G-A
• rs117034794
• NM_021134.4:c.141-8G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_021134.4(MRPL23):​c.141-8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 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 0.00046 (0 hom., cov: 2)
  • Exomes 𝑓: 0.00028 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MRPL23 NM_021134.4 splice_region, intron
• Scores: Splicing: ADA: 0.00008258
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.649
• Publications: 2 publications found

Genes affected

MRPL23 (HGNC:10322): (mitochondrial ribosomal protein L23) 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. The gene is biallelically expressed, despite its location within a region of imprinted genes on chromosome 11. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-1952119-G-A is Benign according to our data. Variant chr11-1952119-G-A is described in ClinVar as [Benign]. Clinvar id is 791542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL23	NM_021134.4	c.141-8G>A		splice_region_variant, intron_variant	Intron 2 of 4	ENST00000397298.8	NP_066957.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL23	ENST00000397298.8	c.141-8G>A		splice_region_variant, intron_variant	Intron 2 of 4	1	NM_021134.4	ENSP00000380466.3

Frequencies

GnomAD3 genomes AF: 0.000456 AC: 8 AN: 17540 Hom.: 0 Cov.: 2

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.0159

Gnomad AMR AF: 0.00101

Gnomad ASJ AF: 0.00181

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000319

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00289 AC: 727 AN: 251328 AF XY: 0.00295

Gnomad AFR exome AF: 0.000862

Gnomad AMR exome AF: 0.00437

Gnomad ASJ exome AF: 0.0129

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000508

Gnomad NFE exome AF: 0.00267

Gnomad OTH exome AF: 0.00767

GnomAD4 exome AF: 0.000277 AC: 27 AN: 97538 Hom.: 0 Cov.: 0 AF XY: 0.000271 AC XY: 14 AN XY: 51684

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 1472

American (AMR) AF: 0.000309 AC: 1 AN: 3232

Ashkenazi Jewish (ASJ) AF: 0.00142 AC: 4 AN: 2818

East Asian (EAS) AF: 0.00 AC: 0 AN: 3460

South Asian (SAS) AF: 0.000222 AC: 2 AN: 9006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6710

Middle Eastern (MID) AF: 0.00701 AC: 3 AN: 428

European-Non Finnish (NFE) AF: 0.000215 AC: 14 AN: 65006

Other (OTH) AF: 0.000555 AC: 3 AN: 5406

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000456 AC: 8 AN: 17554 Hom.: 0 Cov.: 2 AF XY: 0.000258 AC XY: 2 AN XY: 7746

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 1834

American (AMR) AF: 0.00101 AC: 1 AN: 992

Ashkenazi Jewish (ASJ) AF: 0.00181 AC: 1 AN: 552

East Asian (EAS) AF: 0.00 AC: 0 AN: 346

South Asian (SAS) AF: 0.00 AC: 0 AN: 200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 698

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 26

European-Non Finnish (NFE) AF: 0.000319 AC: 4 AN: 12552

Other (OTH) AF: 0.00 AC: 0 AN: 228

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00300 Hom.: 1

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.00382

EpiControl AF: 0.00397

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 12, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.24
DANN	Benign	0.73
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000083
dbscSNV1_RF	Benign	0.014
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

Other links and lift over

dbSNP: rs117034794; hg19: chr11-1973349;