chr2-16555096-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030797.4(CYRIA):​c.881G>A​(p.Ser294Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CYRIA
NM_030797.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.845
Variant links:
Genes affected
CYRIA (HGNC:25373): (CYFIP related Rac1 interactor A) Predicted to enable small GTPase binding activity. Predicted to be involved in regulation of actin filament polymerization. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.07490474).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CYRIANM_030797.4 linkc.881G>A p.Ser294Asn missense_variant Exon 11 of 12 ENST00000381323.7 NP_110424.1 Q9H0Q0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CYRIAENST00000381323.7 linkc.881G>A p.Ser294Asn missense_variant Exon 11 of 12 1 NM_030797.4 ENSP00000370724.3 Q9H0Q0
CYRIAENST00000406434.5 linkc.881G>A p.Ser294Asn missense_variant Exon 12 of 13 5 ENSP00000384771.1 Q9H0Q0
ENSG00000237633ENST00000648675.1 linkn.980-151C>T intron_variant Intron 6 of 6
ENSG00000237633ENST00000667231.1 linkn.628-151C>T intron_variant Intron 5 of 5

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152114
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461108
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726840
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000448
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
AF:
0.00000657
AC:
1
AN:
152114
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74294
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 27, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.881G>A (p.S294N) alteration is located in exon 1 (coding exon 1) of the FAM49A gene. This alteration results from a G to A substitution at nucleotide position 881, causing the serine (S) at amino acid position 294 to be replaced by an asparagine (N). 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
0.080
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.030
T;T
Eigen
Benign
-0.21
Eigen_PC
Benign
-0.053
FATHMM_MKL
Benign
0.41
N
LIST_S2
Benign
0.84
.;T
M_CAP
Benign
0.0043
T
MetaRNN
Benign
0.075
T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Uncertain
2.4
M;M
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-0.40
N;N
REVEL
Benign
0.11
Sift
Benign
0.19
T;T
Sift4G
Benign
0.43
T;T
Polyphen
0.0010
B;B
Vest4
0.070
MutPred
0.47
Loss of phosphorylation at S294 (P = 0.0726);Loss of phosphorylation at S294 (P = 0.0726);
MVP
0.27
MPC
0.96
ClinPred
0.25
T
GERP RS
5.4
Varity_R
0.072
gMVP
0.14

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.

Other links and lift over

dbSNP: rs1485694016; hg19: chr2-16736364; API