Genetic Variant MRPL41:c.*7G>C (chr9-137552502-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_032477.3(MRPL41):c.*7G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00516 in 1,538,358 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0035 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0053 ( 27 hom. )

Consequence

MRPL41
NM_032477.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.486

Variant links:

Genes affected

MRPL41 (HGNC:14492): (mitochondrial ribosomal protein L41) 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 that belongs to the YmL27 ribosomal protein family. [provided by RefSeq, Jul 2008]

MRPL41 links:

LOC124902317 (HGNC:):

LOC124902317 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BS2

High Homozygotes in GnomAdExome4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL41	NM_032477.3 link	c.*7G>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000371443.6	NP_115866.1	Q8IXM3
LOC124902317	XR_007061883.1 link	n.*25C>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL41	ENST00000371443.6 link	c.*7G>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_032477.3	ENSP00000360498.5		Q8IXM3

Frequencies

GnomAD3 genomes

AF:

0.00347

AC:

529

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00549

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00216

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00522

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00334

AC:

629

AN:

188384

Hom.:

AF XY:

0.00347

AC XY:

358

AN XY:

103182

show subpopulations

Gnomad AFR exome

AF:

0.00114

Gnomad AMR exome

AF:

0.00412

Gnomad ASJ exome

AF:

0.00215

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000443

Gnomad FIN exome

AF:

0.00207

Gnomad NFE exome

AF:

0.00499

Gnomad OTH exome

AF:

0.00373

GnomAD4 exome

AF:

0.00535

AC:

7410

AN:

1385990

Hom.:

Cov.:

AF XY:

0.00509

AC XY:

3475

AN XY:

682526

show subpopulations

Gnomad4 AFR exome

AF:

0.00103

Gnomad4 AMR exome

AF:

0.00371

Gnomad4 ASJ exome

AF:

0.00353

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000376

Gnomad4 FIN exome

AF:

0.00221

Gnomad4 NFE exome

AF:

0.00635

Gnomad4 OTH exome

AF:

0.00393

GnomAD4 genome

AF:

0.00347

AC:

529

AN:

152368

Hom.:

Cov.:

AF XY:

0.00321

AC XY:

239

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00549

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00216

Gnomad4 NFE

AF:

0.00522

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00428

Hom.:

Bravo

AF:

0.00356

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over