Genetic Variant RANBP3L:c.*1004A>C (chr5-36248650-T-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001323273.2(RANBP3L):c.1476A>C(p.Leu492Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 152,114 control chromosomes in the GnomAD database, including 59,380 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.87 ( 59380 hom., cov: 31)

Failed GnomAD Quality Control

Consequence

RANBP3L
NM_001323273.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.09

Variant links:

Genes affected

RANBP3L (HGNC:26353): (RAN binding protein 3 like) Enables SMAD binding activity. Predicted to be involved in several processes, including mesenchymal cell differentiation involved in bone development; negative regulation of osteoblast differentiation; and positive regulation of myoblast differentiation. Predicted to be part of nuclear pore. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RANBP3L links:

LOC124900962 (HGNC:):

LOC124900962 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 5-36248650-T-G is Benign according to our data. Variant chr5-36248650-T-G is described in ClinVar as [Benign]. Clinvar id is 2785882.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RANBP3L	NM_145000.5 link	c.*1004A>C		3_prime_UTR_variant	Exon 14 of 14	ENST00000296604.8	NP_659437.3	Q86VV4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RANBP3L	ENST00000296604.8 link	c.*1004A>C		3_prime_UTR_variant	Exon 14 of 14	1	NM_145000.5	ENSP00000296604.3		Q86VV4-1

Frequencies

GnomAD3 genomes

AF:

0.875

AC:

132967

AN:

151996

Hom.:

59360

Cov.:

show subpopulations

Gnomad AFR

AF:

0.701

Gnomad AMI

AF:

0.999

Gnomad AMR

AF:

0.861

Gnomad ASJ

AF:

0.938

Gnomad EAS

AF:

0.691

Gnomad SAS

AF:

0.934

Gnomad FIN

AF:

0.979

Gnomad MID

AF:

0.880

Gnomad NFE

AF:

0.972

Gnomad OTH

AF:

0.893

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.875

AC:

133031

AN:

152114

Hom.:

59380

Cov.:

AF XY:

0.875

AC XY:

65042

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.700

AC:

29023

AN:

41432

American (AMR)

AF:

0.861

AC:

13158

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.938

AC:

3258

AN:

3472

East Asian (EAS)

AF:

0.691

AC:

3573

AN:

5172

South Asian (SAS)

AF:

0.934

AC:

4509

AN:

4826

European-Finnish (FIN)

AF:

0.979

AC:

10383

AN:

10610

Middle Eastern (MID)

AF:

0.871

AC:

256

AN:

294

European-Non Finnish (NFE)

AF:

0.972

AC:

66077

AN:

68004

Other (OTH)

AF:

0.893

AC:

1883

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

734

1468

2203

2937

3671

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.931

Hom.:

168809

Bravo

AF:

0.855

Asia WGS

AF:

0.825

AC:

2868

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: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

-0.90

CADD

Benign

0.86

(source)

DANN

Benign

0.61

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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5-36248650-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over