chr16-60236-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022450.5(RHBDF1):​c.1702G>A​(p.Glu568Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E568Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

RHBDF1
NM_022450.5 missense

Scores

7
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.84
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22907439).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RHBDF1NM_022450.5 linkc.1702G>A p.Glu568Lys missense_variant Exon 13 of 18 ENST00000262316.10 NP_071895.3 Q96CC6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RHBDF1ENST00000262316.10 linkc.1702G>A p.Glu568Lys missense_variant Exon 13 of 18 1 NM_022450.5 ENSP00000262316.5 Q96CC6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.24
T
Eigen
Benign
0.037
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.97
D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.23
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.43
T
PROVEAN
Uncertain
-2.4
N
REVEL
Benign
0.11
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.049
D
Polyphen
0.0010
B
Vest4
0.34
MutPred
0.37
Gain of methylation at E568 (P = 5e-04);
MVP
0.56
MPC
0.42
ClinPred
0.87
D
GERP RS
5.2
Varity_R
0.52
gMVP
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs761217453; hg19: chr16-110234; API