3-131468049-CAAAAAA-CAAAAA

Variant names:

• chr3-131468049-CA-C
• rs56928817
• NM_007208.4:c.894+41delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_007208.4(MRPL3):​c.894+41delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (29785 hom., cov: 0)
  • Exomes 𝑓: 0.47 (27967 hom.)
  • Failed GnomAD Quality Control
• Consequence: MRPL3 NM_007208.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.292
• Publications: 0 publications found

Genes affected

MRPL3 (HGNC:10379): (mitochondrial ribosomal protein L3) 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 L3P ribosomal protein family. A pseudogene corresponding to this gene is found on chromosome 13q. [provided by RefSeq, Jul 2008]

MRPL3 Gene-Disease associations (from GenCC):

• combined oxidative phosphorylation defect type 9

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• mitochondrial disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 3-131468049-CA-C is Benign according to our data. Variant chr3-131468049-CA-C is described in ClinVar as Benign. ClinVar VariationId is 1239761.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007208.4. 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
	MRPL3	NM_007208.4	MANE Select	c.894+41delT		intron	N/A	NP_009139.1	P09001

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL3	ENST00000264995.8	TSL:1 MANE Select	c.894+41delT		intron	N/A	ENSP00000264995.2	P09001
	MRPL3	ENST00000425847.6	TSL:2	c.975+41delT		intron	N/A	ENSP00000398536.2	E7ETU7
	MRPL3	ENST00000511168.5	TSL:2	c.936+41delT		intron	N/A	ENSP00000424107.1	H0Y9G6

Frequencies

GnomAD3 genomes AF: 0.658 AC: 90613 AN: 137620 Hom.: 29757 Cov.: 0

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.653

GnomAD2 exomes AF: 0.516 AC: 58001 AN: 112418 AF XY: 0.509

Gnomad AFR exome AF: 0.692

Gnomad AMR exome AF: 0.506

Gnomad ASJ exome AF: 0.481

Gnomad EAS exome AF: 0.496

Gnomad FIN exome AF: 0.495

Gnomad NFE exome AF: 0.514

Gnomad OTH exome AF: 0.517

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.471 AC: 328236 AN: 697542 Hom.: 27967 Cov.: 0 AF XY: 0.472 AC XY: 169258 AN XY: 358756

African (AFR) AF: 0.615 AC: 7838 AN: 12742

American (AMR) AF: 0.480 AC: 7986 AN: 16642

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 6454 AN: 14136

East Asian (EAS) AF: 0.459 AC: 11408 AN: 24864

South Asian (SAS) AF: 0.442 AC: 16628 AN: 37600

European-Finnish (FIN) AF: 0.485 AC: 18195 AN: 37478

Middle Eastern (MID) AF: 0.532 AC: 1569 AN: 2948

European-Non Finnish (NFE) AF: 0.468 AC: 243693 AN: 520706

Other (OTH) AF: 0.475 AC: 14465 AN: 30426

GnomAD4 genome AF: 0.659 AC: 90662 AN: 137662 Hom.: 29785 Cov.: 0 AF XY: 0.653 AC XY: 43493 AN XY: 66648

African (AFR) AF: 0.875 AC: 34123 AN: 39006

American (AMR) AF: 0.599 AC: 8195 AN: 13676

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1723 AN: 3106

East Asian (EAS) AF: 0.447 AC: 2028 AN: 4532

South Asian (SAS) AF: 0.493 AC: 2049 AN: 4156

European-Finnish (FIN) AF: 0.547 AC: 4412 AN: 8060

Middle Eastern (MID) AF: 0.640 AC: 160 AN: 250

European-Non Finnish (NFE) AF: 0.583 AC: 36217 AN: 62112

Other (OTH) AF: 0.652 AC: 1249 AN: 1916

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: 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
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs56928817; hg19: chr3-131186893; COSMIC: COSV53913619; COSMIC: COSV53913619;