Genetic Variant CYRIB:p.Ser31Pro (chr8-129871479-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001353258.2(CYRIB):c.91T>C(p.Ser31Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,456,846 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: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CYRIB
NM_001353258.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.74

Variant links:

Genes affected

CYRIB (HGNC:25216): (CYFIP related Rac1 interactor B) Enables small GTPase binding activity. Involved in several processes, including cellular response to molecule of bacterial origin; negative regulation of small GTPase mediated signal transduction; and regulation of organelle organization. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

CYRIB links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32007563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYRIB	NM_001353258.2 link	c.91T>C	p.Ser31Pro	missense_variant	Exon 6 of 14	ENST00000694912.1	NP_001340187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYRIB	ENST00000694912.1 link	c.91T>C	p.Ser31Pro	missense_variant	Exon 6 of 14		NM_001353258.2	ENSP00000511587.1		Q9NUQ9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000811

AC:

AN:

246512

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133266

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:

0.0000680

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1456846

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

724382

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:

0.0000474

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.91T>C (p.S31P) alteration is located in exon 7 (coding exon 2) of the FAM49B gene. This alteration results from a T to C substitution at nucleotide position 91, causing the serine (S) at amino acid position 31 to be replaced by a proline (P). 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

0.19

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.047

T;T;T;T;T;T;T;T;T;.;.;T;T;T;T;.;.

Eigen

Benign

-0.023

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

.;.;.;.;.;.;T;T;T;T;T;T;T;T;D;T;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.32

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;M;M;M;M;M;M;.;.;.;.;.;.;.;.;.;.

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.3

N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.27

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;D

Sift4G

Benign

0.25

T;T;T;T;T;T;T;.;.;.;.;.;T;T;T;.;.

Polyphen

0.0010

B;B;B;B;B;B;B;.;.;.;.;.;.;.;.;.;.

Vest4

0.31

MutPred

0.46

Gain of glycosylation at S31 (P = 0.0284);Gain of glycosylation at S31 (P = 0.0284);Gain of glycosylation at S31 (P = 0.0284);Gain of glycosylation at S31 (P = 0.0284);Gain of glycosylation at S31 (P = 0.0284);Gain of glycosylation at S31 (P = 0.0284);Gain of glycosylation at S31 (P = 0.0284);Gain of glycosylation at S31 (P = 0.0284);Gain of glycosylation at S31 (P = 0.0284);Gain of glycosylation at S31 (P = 0.0284);Gain of glycosylation at S31 (P = 0.0284);Gain of glycosylation at S31 (P = 0.0284);Gain of glycosylation at S31 (P = 0.0284);Gain of glycosylation at S31 (P = 0.0284);Gain of glycosylation at S31 (P = 0.0284);Gain of glycosylation at S31 (P = 0.0284);Gain of glycosylation at S31 (P = 0.0284);

MVP

0.33

MPC

1.4

ClinPred

0.22

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.34

gMVP

0.90

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

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