Variant chr17-32266281-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_138328.3(RHBDL3):c.92T>C(p.Leu31Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RHBDL3
NM_138328.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.672

Variant links:

Genes affected

RHBDL3 (HGNC:16502): (rhomboid like 3) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

RHBDL3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1359157).

BP6

Variant 17-32266281-T-C is Benign according to our data. Variant chr17-32266281-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2569506.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHBDL3	NM_138328.3 linkuse as main transcript	c.92T>C	p.Leu31Pro	missense_variant	1/9	ENST00000269051.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHBDL3	ENST00000269051.9 linkuse as main transcript	c.92T>C	p.Leu31Pro	missense_variant	1/9	1	NM_138328.3	P1	P58872-1
RHBDL3	ENST00000431505.6 linkuse as main transcript	c.92T>C	p.Leu31Pro	missense_variant	1/8	1
RHBDL3	ENST00000538145.5 linkuse as main transcript	c.92T>C	p.Leu31Pro	missense_variant	1/8	1			P58872-3
RHBDL3	ENST00000578006.5 linkuse as main transcript	c.92T>C	p.Leu31Pro	missense_variant, NMD_transcript_variant	1/9	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1315474

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

648556

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.024

T;T;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.51

T;T;T

M_CAP

Pathogenic

0.50

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

.;L;L

MutationTaster

Benign

0.62

N;N

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.084

Sift

Uncertain

0.010

D;D;D

Sift4G

Uncertain

0.018

D;T;D

Polyphen

0.0

.;B;.

Vest4

0.11, 0.13

MutPred

0.41

Gain of glycosylation at L31 (P = 0.0076);Gain of glycosylation at L31 (P = 0.0076);Gain of glycosylation at L31 (P = 0.0076);

MVP

0.33

MPC

1.1

ClinPred

0.38

GERP RS

-0.80

Varity_R

0.37

gMVP

0.63

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over