8-129852272-C-T

Variant names:

• chr8-129852272-C-T
• rs370641130
• NM_001353258.2:c.523G>A

Variant summary

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

The NM_001353258.2(CYRIB):​c.523G>A​(p.Gly175Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000604 in 1,556,668 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: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000064 (0 hom.)
• Consequence: CYRIB NM_001353258.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.78
• Publications: 3 publications found

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]

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=0.17951602).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353258.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYRIB	NM_001353258.2	MANE Select	c.523G>A	p.Gly175Arg	missense	Exon 10 of 14	NP_001340187.1	Q9NUQ9-1
	CYRIB	NM_001256763.2		c.523G>A	p.Gly175Arg	missense	Exon 9 of 13	NP_001243692.1	Q9NUQ9-1
	CYRIB	NM_001353242.2		c.523G>A	p.Gly175Arg	missense	Exon 11 of 15	NP_001340171.1	Q9NUQ9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYRIB	ENST00000694912.1	MANE Select	c.523G>A	p.Gly175Arg	missense	Exon 10 of 14	ENSP00000511587.1	Q9NUQ9-1
	CYRIB	ENST00000519540.5	TSL:1	c.523G>A	p.Gly175Arg	missense	Exon 9 of 13	ENSP00000429499.1	Q9NUQ9-1
	CYRIB	ENST00000522746.5	TSL:1	c.523G>A	p.Gly175Arg	missense	Exon 11 of 15	ENSP00000428117.1	Q9NUQ9-1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152186 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000187 AC: 4 AN: 214322 AF XY: 0.00000858

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: 0.0000398

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000641 AC: 90 AN: 1404482 Hom.: 0 Cov.: 28 AF XY: 0.0000573 AC XY: 40 AN XY: 698092

African (AFR) AF: 0.0000322 AC: 1 AN: 31104

American (AMR) AF: 0.00 AC: 0 AN: 37168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24262

East Asian (EAS) AF: 0.00 AC: 0 AN: 36742

South Asian (SAS) AF: 0.00 AC: 0 AN: 77982

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51926

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5580

European-Non Finnish (NFE) AF: 0.0000730 AC: 79 AN: 1082158

Other (OTH) AF: 0.000174 AC: 10 AN: 57560

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152186 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000735 Hom.: 0

Bravo AF: 0.0000189

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.0095
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.8
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.050
Sift	Benign	0.49	T
Sift4G	Benign	0.52	T
Polyphen		0.0070	B
Vest4		0.38
MutPred		0.37		Gain of disorder (P = 0.0443)
MVP		0.082
MPC		1.3
ClinPred		0.17	T
GERP RS		6.0
Varity_R		0.084
gMVP		0.75
Mutation Taster		=65/35	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: rs370641130; hg19: chr8-130864518; COSMIC: COSV67828286; COSMIC: COSV67828286;