2-75655055-C-T

Variant names:

• chr2-75655055-C-T
• rs775408727
• NM_014763.4:c.658-9C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_014763.4(MRPL19):​c.658-9C>T variant causes a 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 0.0098 (0 hom., cov: 22)
  • Exomes 𝑓: 0.011 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: MRPL19 NM_014763.4 intron
• Scores: Splicing: ADA: 0.00004051
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.574
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 2-75655055-C-T is Benign according to our data. Variant chr2-75655055-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 769565.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014763.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL19	NM_014763.4	MANE Select	c.658-9C>T		intron	N/A	NP_055578.2	P49406

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL19	ENST00000393909.7	TSL:1 MANE Select	c.658-9C>T		intron	N/A	ENSP00000377486.2	P49406
	MRPL19	ENST00000409374.5	TSL:5	c.658-9C>T		intron	N/A	ENSP00000387284.1	P49406
	MRPL19	ENST00000884931.1		c.658-9C>T		intron	N/A	ENSP00000554990.1

Frequencies

GnomAD3 genomes AF: 0.00976 AC: 775 AN: 79386 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00978

Gnomad AMI AF: 0.0151

Gnomad AMR AF: 0.00899

Gnomad ASJ AF: 0.00386

Gnomad EAS AF: 0.00573

Gnomad SAS AF: 0.00591

Gnomad FIN AF: 0.0342

Gnomad MID AF: 0.0246

Gnomad NFE AF: 0.00853

Gnomad OTH AF: 0.0101

GnomAD2 exomes AF: 0.00938 AC: 1074 AN: 114478 AF XY: 0.00865

Gnomad AFR exome AF: 0.0134

Gnomad AMR exome AF: 0.0123

Gnomad ASJ exome AF: 0.00735

Gnomad EAS exome AF: 0.0214

Gnomad FIN exome AF: 0.00673

Gnomad NFE exome AF: 0.00767

Gnomad OTH exome AF: 0.0197

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0110 AC: 6938 AN: 630838 Hom.: 1 Cov.: 19 AF XY: 0.0120 AC XY: 3811 AN XY: 318736

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

African (AFR) AF: 0.0164 AC: 223 AN: 13590

American (AMR) AF: 0.0220 AC: 352 AN: 15968

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 198 AN: 12980

East Asian (EAS) AF: 0.0163 AC: 394 AN: 24234

South Asian (SAS) AF: 0.0434 AC: 1325 AN: 30512

European-Finnish (FIN) AF: 0.0137 AC: 508 AN: 37080

Middle Eastern (MID) AF: 0.0148 AC: 30 AN: 2026

European-Non Finnish (NFE) AF: 0.00766 AC: 3574 AN: 466854

Other (OTH) AF: 0.0121 AC: 334 AN: 27594

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00976 AC: 775 AN: 79430 Hom.: 0 Cov.: 22 AF XY: 0.0105 AC XY: 394 AN XY: 37580

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

African (AFR) AF: 0.00975 AC: 213 AN: 21842

American (AMR) AF: 0.00912 AC: 65 AN: 7124

Ashkenazi Jewish (ASJ) AF: 0.00386 AC: 8 AN: 2074

East Asian (EAS) AF: 0.00575 AC: 14 AN: 2434

South Asian (SAS) AF: 0.00593 AC: 14 AN: 2362

European-Finnish (FIN) AF: 0.0342 AC: 111 AN: 3248

Middle Eastern (MID) AF: 0.0175 AC: 2 AN: 114

European-Non Finnish (NFE) AF: 0.00850 AC: 328 AN: 38576

Other (OTH) AF: 0.0109 AC: 13 AN: 1192

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0178 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Benign	0.73
PhyloP100		0.57
PromoterAI		0.0053	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000041
dbscSNV1_RF	Benign	0.0
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: rs775408727; hg19: chr2-75882181; COSMIC: COSV62567746; COSMIC: COSV62567746;