rs765019295

chr19-10259604-A-Cchr19-10259604-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_015956.3(MRPL4):c.740-13A>C 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (0 hom., cov: 0)
  • Exomes 𝑓: 0.12 (240 hom.)
  • Failed GnomAD Quality Control
• Consequence: MRPL4 NM_015956.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.623

Genes affected

MRPL4 (HGNC:14276): (mitochondrial ribosomal protein L4) 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. Sequence analysis identified alternatively spliced variants that encode different protein isoforms. [provided by RefSeq, Jul 2008]

(HGNC:):

LIMASI (HGNC:56357): (lncRNA inflammatory and mucous response associated, antisense to ICAM1)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 19-10259604-A-C is Benign according to our data. Variant chr19-10259604-A-C is described in ClinVar as [Benign]. Clinvar id is 403106.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 59 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL4	NM_015956.3	c.740-13A>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000253099.11
MRPL4	NM_001411149.1	c.*98A>C		3_prime_UTR_variant	9/9
MRPL4	NM_146388.2	c.*866A>C		3_prime_UTR_variant	8/8
MRPL4	NM_146387.2	c.740-13A>C		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL4	ENST00000253099.11	c.740-13A>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_015956.3	P1
	ENST00000587088.1	n.222+220T>G		intron_variant, non_coding_transcript_variant		2
LIMASI	ENST00000592893.1	n.358+608T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 8001 AN: 24390 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.167

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.329

GnomAD3 exomes AF: 0.431 AC: 23374 AN: 54276 Hom.: 59 AF XY: 0.430 AC XY: 12758 AN XY: 29658

Gnomad AFR exome AF: 0.383

Gnomad AMR exome AF: 0.462

Gnomad ASJ exome AF: 0.484

Gnomad EAS exome AF: 0.435

Gnomad SAS exome AF: 0.476

Gnomad FIN exome AF: 0.448

Gnomad NFE exome AF: 0.393

Gnomad OTH exome AF: 0.454

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.121 AC: 37853 AN: 311844 Hom.: 240 Cov.: 26 AF XY: 0.137 AC XY: 20729 AN XY: 151840

Gnomad4 AFR exome AF: 0.173

Gnomad4 AMR exome AF: 0.446

Gnomad4 ASJ exome AF: 0.307

Gnomad4 EAS exome AF: 0.199

Gnomad4 SAS exome AF: 0.340

Gnomad4 FIN exome AF: 0.337

Gnomad4 NFE exome AF: 0.0749

Gnomad4 OTH exome AF: 0.148

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.328 AC: 8002 AN: 24406 Hom.: 0 Cov.: 0 AF XY: 0.300 AC XY: 3651 AN XY: 12160

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.327

Alfa AF: 0.00374 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.1
Dann	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs765019295; hg19: chr19-10370280; COSMIC: COSV53448098; COSMIC: COSV53448098;