rs765019295

Variant names:

• chr19-10259604-A-C
• rs765019295
• NM_015956.3:c.740-13A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-10259604-A-C
• chr19-10259604-A-G

Variant summary

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

The NM_001411149.1(MRPL4):​c.*98A>C variant causes a 3 prime UTR 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_001411149.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.623
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -12 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 VariationId is 403106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001411149.1. 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
	MRPL4	NM_015956.3	MANE Select	c.740-13A>C		intron	N/A	NP_057040.2
	MRPL4	NM_001411149.1		c.*98A>C		3_prime_UTR	Exon 9 of 9	NP_001398078.1	X6RAY8
	MRPL4	NM_146388.2		c.*866A>C		3_prime_UTR	Exon 8 of 8	NP_666500.1	Q9BYD3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL4	ENST00000253099.11	TSL:1 MANE Select	c.740-13A>C		intron	N/A	ENSP00000253099.5	Q9BYD3-1
	MRPL4	ENST00000393733.6	TSL:5	c.*98A>C		3_prime_UTR	Exon 9 of 9	ENSP00000377334.2	X6RAY8
	MRPL4	ENST00000930030.1		c.914-13A>C		intron	N/A	ENSP00000600089.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 8001 AN: 24390 Hom.: 0 Cov.: 0

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

GnomAD2 exomes AF: 0.431 AC: 23374 AN: 54276 AF XY: 0.430

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 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

African (AFR) AF: 0.173 AC: 1379 AN: 7974

American (AMR) AF: 0.446 AC: 4611 AN: 10346

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1402 AN: 4566

East Asian (EAS) AF: 0.199 AC: 1290 AN: 6498

South Asian (SAS) AF: 0.340 AC: 6723 AN: 19780

European-Finnish (FIN) AF: 0.337 AC: 2393 AN: 7104

Middle Eastern (MID) AF: 0.165 AC: 123 AN: 746

European-Non Finnish (NFE) AF: 0.0749 AC: 18209 AN: 243196

Other (OTH) AF: 0.148 AC: 1723 AN: 11634

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

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

African (AFR) AF: 0.302 AC: 2059 AN: 6828

American (AMR) AF: 0.193 AC: 637 AN: 3294

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 209 AN: 522

East Asian (EAS) AF: 0.297 AC: 117 AN: 394

South Asian (SAS) AF: 0.319 AC: 144 AN: 452

European-Finnish (FIN) AF: 0.207 AC: 406 AN: 1966

Middle Eastern (MID) AF: 0.167 AC: 5 AN: 30

European-Non Finnish (NFE) AF: 0.408 AC: 4278 AN: 10498

Other (OTH) AF: 0.327 AC: 115 AN: 352

⚠️ 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: 0.00374 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.68
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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