Variant 16-61130-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022450.5(RHBDF1):c.1547A>G(p.Glu516Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,378,822 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

RHBDF1
NM_022450.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.94

Variant links:

Genes affected

RHBDF1 (HGNC:20561): (rhomboid 5 homolog 1) Predicted to enable growth factor binding activity and serine-type endopeptidase activity. Involved in several processes, including negative regulation of protein secretion; regulation of epidermal growth factor receptor signaling pathway; and regulation of proteasomal protein catabolic process. Located in Golgi membrane and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

RHBDF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHBDF1	NM_022450.5 link	c.1547A>G	p.Glu516Gly	missense_variant	11/18	ENST00000262316.10	NP_071895.3	Q96CC6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RHBDF1	ENST00000262316.10 link	c.1547A>G	p.Glu516Gly	missense_variant	11/18	1	NM_022450.5	ENSP00000262316.5	Q96CC6
RHBDF1	ENST00000428730.5 link	n.*861A>G		non_coding_transcript_exon_variant	10/17	5		ENSP00000411508.1	F8WBS4
RHBDF1	ENST00000428730.5 link	n.*861A>G		3_prime_UTR_variant	10/17	5		ENSP00000411508.1	F8WBS4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000719

AC:

AN:

139048

Hom.:

AF XY:

0.00

AC XY:

AN XY:

74906

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000186

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1378822

Hom.:

Cov.:

AF XY:

0.00000737

AC XY:

AN XY:

678674

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000149

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 13, 2023

The c.1547A>G (p.E516G) alteration is located in exon 11 (coding exon 10) of the RHBDF1 gene. This alteration results from a A to G substitution at nucleotide position 1547, causing the glutamic acid (E) at amino acid position 516 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Benign

0.93

DEOGEN2

Benign

0.17

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.23

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.61

M_CAP

Benign

0.021

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.31

Sift

Benign

0.058

Sift4G

Benign

0.24

Polyphen

0.0

Vest4

0.49

MutPred

0.31

Gain of loop (P = 0.0097);

MVP

0.46

MPC

0.41

ClinPred

0.82

GERP RS

4.2

Varity_R

0.23

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.49

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.49

Position offset: 27

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over