2-157416029-T-C

Variant names:

• chr2-157416029-T-C
• NM_004288.5:c.728A>G

Variant summary

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

The NM_004288.5(CYTIP):​c.728A>G​(p.Glu243Gly) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CYTIP NM_004288.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.07

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]

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=0.07156673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYTIP	NM_004288.5	c.728A>G	p.Glu243Gly	missense_variant	Exon 8 of 8	ENST00000264192.8	NP_004279.3
CYTIP	XM_017005386.3	c.410A>G	p.Glu137Gly	missense_variant	Exon 8 of 8		XP_016860875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYTIP	ENST00000264192.8	c.728A>G	p.Glu243Gly	missense_variant	Exon 8 of 8	1	NM_004288.5	ENSP00000264192.3
CYTIP	ENST00000418920.5	c.*17A>G		downstream_gene_variant		5		ENSP00000394308.1
CYTIP	ENST00000457793.6	n.*623A>G		downstream_gene_variant		5		ENSP00000407205.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.728A>G (p.E243G) alteration is located in exon 8 (coding exon 8) of the CYTIP gene. This alteration results from a A to G substitution at nucleotide position 728, causing the glutamic acid (E) at amino acid position 243 to be replaced by a glycine (G). 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	0.14
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.031
Sift	Benign	0.29	T
Sift4G	Benign	0.32	T
Polyphen		0.0	B
Vest4		0.062
MutPred		0.24		Gain of glycosylation at S242 (P = 0.0271);
MVP		0.18
MPC		0.19
ClinPred		0.098	T
GERP RS		-0.051
Varity_R		0.072
gMVP		0.29

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: chr2-158272541;