2-75655055-C-A

Position:

• chr2-75655055-C-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_014763.4(MRPL19):​c.658-9C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 22)
  • Exomes 𝑓: 0.046 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MRPL19 NM_014763.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0006152
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.574

Genes affected

MRPL19 (HGNC:14052): (mitochondrial ribosomal protein L19) 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]

GCFC2 (HGNC:1317): (GC-rich sequence DNA-binding factor 2) The first mRNA transcript isolated for this gene was part of an artificial chimera derived from two distinct gene transcripts and a primer used in the cloning process (see Genbank accession M29204). A positively charged amino terminus present only in the chimera was determined to bind GC-rich DNA, thus mistakenly thought to identify a transcription factor gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 2-75655055-C-A is Benign according to our data. Variant chr2-75655055-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 726493.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL19	NM_014763.4	c.658-9C>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000393909.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL19	ENST00000393909.7	c.658-9C>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_014763.4	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 148 AN: 81104 Hom.: 0 Cov.: 22 FAILED QC

Gnomad AFR AF: 0.00206

Gnomad AMI AF: 0.00211

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00842

Gnomad SAS AF: 0.00586

Gnomad FIN AF: 0.00362

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000889

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0459 AC: 28684 AN: 624820 Hom.: 0 Cov.: 19 AF XY: 0.0440 AC XY: 13937 AN XY: 316728

Gnomad4 AFR exome AF: 0.0456

Gnomad4 AMR exome AF: 0.0180

Gnomad4 ASJ exome AF: 0.0294

Gnomad4 EAS exome AF: 0.0298

Gnomad4 SAS exome AF: 0.0158

Gnomad4 FIN exome AF: 0.0164

Gnomad4 NFE exome AF: 0.0530

Gnomad4 OTH exome AF: 0.0419

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00184 AC: 149 AN: 81148 Hom.: 0 Cov.: 22 AF XY: 0.00209 AC XY: 80 AN XY: 38306

Gnomad4 AFR AF: 0.00219

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00805

Gnomad4 SAS AF: 0.00588

Gnomad4 FIN AF: 0.00362

Gnomad4 NFE AF: 0.000889

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00062
dbscSNV1_RF	Benign	0.042
SpliceAI score (max)		0.14		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: rs775408727; hg19: chr2-75882181;