NM_004288.5:c.827G>A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004288.5(CYTIP):​c.827G>A​(p.Arg276Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000564 in 1,614,218 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R276W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000060 ( 3 hom. )

Consequence

CYTIP
NM_004288.5 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.87
Variant links:
Genes affected
CYTIP (HGNC:9506): (cytohesin 1 interacting protein) The protein encoded by this gene contains 2 leucine zipper domains and a putative C-terminal nuclear targeting signal, but does not have any hydrophobic regions. This protein is expressed weakly in resting NK and T cells. The encoded protein modulates the activation of ARF genes by CYTH1. This protein interacts with CYTH1 and SNX27 proteins and may act to sequester CYTH1 protein in the cytoplasm.[provided by RefSeq, Aug 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.100403965).
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CYTIPNM_004288.5 linkc.827G>A p.Arg276Gln missense_variant Exon 8 of 8 ENST00000264192.8 NP_004279.3 O60759-1
CYTIPXM_017005386.3 linkc.509G>A p.Arg170Gln missense_variant Exon 8 of 8 XP_016860875.1 O60759-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CYTIPENST00000264192.8 linkc.827G>A p.Arg276Gln missense_variant Exon 8 of 8 1 NM_004288.5 ENSP00000264192.3 O60759-1
CYTIPENST00000418920.5 linkc.*116G>A downstream_gene_variant 5 ENSP00000394308.1 C9JSM2
CYTIPENST00000457793.6 linkn.*722G>A downstream_gene_variant 5 ENSP00000407205.2 F8WF61

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152214
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000123
AC:
31
AN:
251146
Hom.:
1
AF XY:
0.000155
AC XY:
21
AN XY:
135704
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000947
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000602
AC:
88
AN:
1461886
Hom.:
3
Cov.:
31
AF XY:
0.0000866
AC XY:
63
AN XY:
727246
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:
0.000916
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152332
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.0000240
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000104
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.0000659
AC:
8
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 02, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.827G>A (p.R276Q) alteration is located in exon 8 (coding exon 8) of the CYTIP gene. This alteration results from a G to A substitution at nucleotide position 827, causing the arginine (R) at amino acid position 276 to be replaced by a glutamine (Q). 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
0.13
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Uncertain
-0.070
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.30
T
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-0.81
T
MutationAssessor
Uncertain
2.1
M
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.18
Sift
Benign
0.19
T
Sift4G
Benign
0.36
T
Polyphen
1.0
D
Vest4
0.29
MVP
0.41
MPC
0.72
ClinPred
0.24
T
GERP RS
6.0
Varity_R
0.091
gMVP
0.31

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: rs199714967; hg19: chr2-158272442; API