Variant 4-5015176-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018659.3(CYTL1):c.386C>T(p.Thr129Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,860 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 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

CYTL1
NM_018659.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.939

Variant links:

Genes affected

CYTL1 (HGNC:24435): (cytokine like 1) C17 is a cytokine-like protein specifically expressed in bone marrow and cord blood mononuclear cells that bear the CD34 (MIM 142230) surface marker (Liu et al., 2000 [PubMed 10857752]).[supplied by OMIM, Mar 2008]

CYTL1 links:

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=0.15662512).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYTL1	NM_018659.3 linkuse as main transcript	c.386C>T	p.Thr129Met	missense_variant	4/4	ENST00000307746.9	NP_061129.1
CYTL1	XM_017008299.2 linkuse as main transcript	c.*36C>T		3_prime_UTR_variant	5/5		XP_016863788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CYTL1	ENST00000307746.9 linkuse as main transcript	c.386C>T	p.Thr129Met	missense_variant	4/4	1	NM_018659.3	ENSP00000303550	P1
CYTL1	ENST00000509419.1 linkuse as main transcript	c.254C>T	p.Thr85Met	missense_variant	3/3	3		ENSP00000421743
CYTL1	ENST00000506508.1 linkuse as main transcript	c.206C>T	p.Thr69Met	missense_variant	2/2	3		ENSP00000425397

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152178

Hom.:

Cov.:

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251228

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1461564

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727054

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000109

EpiControl

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2023

The c.386C>T (p.T129M) alteration is located in exon 4 (coding exon 4) of the CYTL1 gene. This alteration results from a C to T substitution at nucleotide position 386, causing the threonine (T) at amino acid position 129 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

0.11

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Benign

0.11

Eigen_PC

Benign

-0.064

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.68

M_CAP

Benign

0.0067

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.082

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.12

MVP

0.30

MPC

0.29

ClinPred

0.30

GERP RS

4.4

Varity_R

0.13

gMVP

0.44

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over