2-157430900-T-C

Variant names:

• chr2-157430900-T-C
• NM_004288.5:c.342A>G

Variant summary

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

The NM_004288.5(CYTIP):​c.342A>G​(p.Ile114Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 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: -0.579

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYTIP	NM_004288.5	c.342A>G	p.Ile114Met	missense_variant	Exon 4 of 8	ENST00000264192.8	NP_004279.3
CYTIP	XM_017005386.3	c.24A>G	p.Ile8Met	missense_variant	Exon 4 of 8		XP_016860875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYTIP	ENST00000264192.8	c.342A>G	p.Ile114Met	missense_variant	Exon 4 of 8	1	NM_004288.5	ENSP00000264192.3

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

Mar 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.342A>G (p.I114M) alteration is located in exon 4 (coding exon 4) of the CYTIP gene. This alteration results from a A to G substitution at nucleotide position 342, causing the isoleucine (I) at amino acid position 114 to be replaced by a methionine (M). 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	0.28
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.0070	T
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.22
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.79	P;.
Vest4		0.64
MutPred		0.74		Gain of catalytic residue at I114 (P = 0.0155);.;
MVP		0.27
MPC		0.47
ClinPred		0.98	D
GERP RS		-3.0
Varity_R		0.56
gMVP		0.67

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: chr2-158287412;