rs143313030

Variant names:

• chr2-226914235-C-A
• rs143313030
• NM_001167608.3:c.740C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-226914235-C-A
• chr2-226914235-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001167608.3(RHBDD1):​c.740C>A​(p.Pro247Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. P247L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: RHBDD1 NM_001167608.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.838
• Publications: 0 publications found

Genes affected

RHBDD1 (HGNC:23081): (rhomboid domain containing 1) Enables serine-type endopeptidase activity. Involved in several processes, including cellular response to unfolded protein; membrane protein proteolysis; and positive regulation of protein catabolic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08155063).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHBDD1	NM_001167608.3	c.740C>A	p.Pro247Gln	missense_variant	Exon 8 of 9	ENST00000392062.7	NP_001161080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHBDD1	ENST00000392062.7	c.740C>A	p.Pro247Gln	missense_variant	Exon 8 of 9	5	NM_001167608.3	ENSP00000375914.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250822 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461456 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727034

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111722

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	7.7
DANN	Benign	0.90
DEOGEN2	Benign	0.0036	T;T;T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.57	.;T;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.082	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L;L;.
PhyloP100		0.84
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.35	N;N;N
REVEL	Benign	0.097
Sift	Benign	0.31	T;T;T
Sift4G	Benign	0.17	T;T;T
Polyphen		0.40	B;B;.
Vest4		0.24
MutPred		0.22		Gain of solvent accessibility (P = 0.0202);Gain of solvent accessibility (P = 0.0202);.;
MVP		0.21
MPC		0.048
ClinPred		0.18	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.051
gMVP		0.72
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs143313030; hg19: chr2-227778951;