Variant 4-5015155-C-T 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.407G>A(p.Arg136His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. R136C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

CYTL1
NM_018659.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.127

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=0.0795297).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYTL1	NM_018659.3 linkuse as main transcript	c.407G>A	p.Arg136His	missense_variant	4/4	ENST00000307746.9	NP_061129.1
CYTL1	XM_017008299.2 linkuse as main transcript	c.*57G>A		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.407G>A	p.Arg136His	missense_variant	4/4	1	NM_018659.3	ENSP00000303550	P1
CYTL1	ENST00000509419.1 linkuse as main transcript	c.275G>A	p.Arg92His	missense_variant	3/3	3		ENSP00000421743
CYTL1	ENST00000506508.1 linkuse as main transcript	c.227G>A	p.Arg76His	missense_variant	2/2	3		ENSP00000425397

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251204

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135716

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:

0.0000462

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1461362

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726962

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000250

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.00491

AC:

AN:

3478

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

May 25, 2022

The c.407G>A (p.R136H) alteration is located in exon 4 (coding exon 4) of the CYTL1 gene. This alteration results from a G to A substitution at nucleotide position 407, causing the arginine (R) at amino acid position 136 to be replaced by a histidine (H). 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

0.12

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.66

M_CAP

Benign

0.0077

MetaRNN

Benign

0.080

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.3

REVEL

Benign

0.038

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.95

Vest4

0.13

MutPred

0.26

Gain of disorder (P = 0.1454);

MVP

0.14

MPC

0.68

ClinPred

0.18

GERP RS

2.3

Varity_R

0.070

gMVP

0.35

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