Genetic Variant ENST00000363046.2:n.269T>C (chr9-35657751-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The ENST00000363046.2(RMRP):n.269T>C variant causes a splice region, non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00037 in 683,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

RMRP
ENST00000363046.2 splice_region, non_coding_transcript_exon

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -8.06

Publications

0 publications found

Variant links:

Genes affected

RMRP (HGNC:10031): (RNA component of mitochondrial RNA processing endoribonuclease) This gene encodes the RNA component of mitochondrial RNA processing endoribonuclease, which cleaves mitochondrial RNA at a priming site of mitochondrial DNA replication. This RNA also interacts with the telomerase reverse transcriptase catalytic subunit to form a distinct ribonucleoprotein complex that has RNA-dependent RNA polymerase activity and produces double-stranded RNAs that can be processed into small interfering RNA. Mutations in this gene are associated with cartilage-hair hypoplasia.[provided by RefSeq, Mar 2010]

RMRP Gene-Disease associations (from GenCC):

cartilage-hair hypoplasia
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Myriad Women’s Health, G2P

RMRP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 9-35657751-A-G is Benign according to our data. Variant chr9-35657751-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 465210.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RMRP	NR_003051.4 link	n.269T>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RMRP	ENST00000363046.2 link	n.269T>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

AF:

0.00103

AC:

157

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00352

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000269

AC:

AN:

122628

AF XY:

0.000239

show subpopulations

Gnomad AFR exome

AF:

0.00412

Gnomad AMR exome

AF:

0.000211

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000193

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000181

AC:

AN:

531208

Hom.:

Cov.:

AF XY:

0.000140

AC XY:

AN XY:

285452

show subpopulations

African (AFR)

AF:

0.00421

AC:

AN:

15456

American (AMR)

AF:

0.000323

AC:

AN:

34014

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19312

East Asian (EAS)

AF:

0.0000944

AC:

AN:

31788

South Asian (SAS)

AF:

0.0000163

AC:

AN:

61488

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32774

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2384

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

304420

Other (OTH)

AF:

0.000237

AC:

AN:

29572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00103

AC:

157

AN:

152338

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.00351

AC:

146

AN:

41582

American (AMR)

AF:

0.000457

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68032

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00110

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Anauxetic dysplasia

Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.22

(source)

DANN

Benign

0.59

PhyloP100

-8.1

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over