8-129855734-T-G

Position:

• chr8-129855734-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001353258.2(CYRIB):​c.315A>C​(p.Arg105Ser) 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. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CYRIB NM_001353258.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.260

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 (HGNC:):

ACMG classification

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=0.16046292).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYRIB	NM_001353258.2	c.315A>C	p.Arg105Ser	missense_variant	8/14	ENST00000694912.1	NP_001340187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYRIB	ENST00000694912.1	c.315A>C	p.Arg105Ser	missense_variant	8/14		NM_001353258.2	ENSP00000511587.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2024

The c.315A>C (p.R105S) alteration is located in exon 9 (coding exon 4) of the FAM49B gene. This alteration results from a A to C substitution at nucleotide position 315, causing the arginine (R) at amino acid position 105 to be replaced by a serine (S). 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	Uncertain	0.45
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T;T;T;T;T;T;T;T
Eigen	Benign	-0.19
Eigen_PC	Benign	0.028
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Pathogenic	0.99	.;.;.;.;.;.;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.16	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L;L;L;L;L;L;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.27	N;N;N;N;N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.13	T;T;T;T;T;T;T;T
Sift4G	Benign	0.081	T;T;T;T;T;T;T;.
Polyphen		0.035	B;B;B;B;B;B;B;.
Vest4		0.48
MutPred		0.52		Gain of glycosylation at R105 (P = 0.0288);Gain of glycosylation at R105 (P = 0.0288);Gain of glycosylation at R105 (P = 0.0288);Gain of glycosylation at R105 (P = 0.0288);Gain of glycosylation at R105 (P = 0.0288);Gain of glycosylation at R105 (P = 0.0288);Gain of glycosylation at R105 (P = 0.0288);Gain of glycosylation at R105 (P = 0.0288);
MVP		0.36
MPC		1.4
ClinPred		0.36	T
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.47

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.

Other links and lift over

hg19: chr8-130867980;