Variant 10-50813874-T-C 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_014576.4(A1CF):c.1306A>G(p.Ile436Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000253 in 1,461,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

A1CF
NM_014576.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.52

Variant links:

Genes affected

A1CF (HGNC:24086): (APOBEC1 complementation factor) Mammalian apolipoprotein B mRNA undergoes site-specific C to U deamination, which is mediated by a multi-component enzyme complex containing a minimal core composed of APOBEC-1 and a complementation factor encoded by this gene. The gene product has three non-identical RNA recognition motifs and belongs to the hnRNP R family of RNA-binding proteins. It has been proposed that this complementation factor functions as an RNA-binding subunit and docks APOBEC-1 to deaminate the upstream cytidine. Studies suggest that the protein may also be involved in other RNA editing or RNA processing events. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

A1CF links:

ASAH2B (HGNC:23456): (N-acylsphingosine amidohydrolase 2B) Predicted to enable N-acylsphingosine amidohydrolase activity. Predicted to be involved in ceramide catabolic process; long-chain fatty acid biosynthetic process; and sphingosine biosynthetic process. Predicted to be active in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ASAH2B links:

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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=0.13656569).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
A1CF	NM_014576.4 linkuse as main transcript	c.1306A>G	p.Ile436Val	missense_variant	10/13	ENST00000373997.8	NP_055391.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
A1CF	ENST00000373997.8 linkuse as main transcript	c.1306A>G	p.Ile436Val	missense_variant	10/13	1	NM_014576.4	ENSP00000363109	A1	Q9NQ94-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251244

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000253

AC:

AN:

1461542

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ExAC

AF:

0.00000824

AC:

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

Nov 08, 2022

The c.1354A>G (p.I452V) alteration is located in exon 12 (coding exon 8) of the A1CF gene. This alteration results from a A to G substitution at nucleotide position 1354, causing the isoleucine (I) at amino acid position 452 to be replaced by a valine (V). 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

0.098

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.099

.;.;.;.;T;.;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.079

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.80

.;T;T;T;T;.;.

M_CAP

Benign

0.0043

MetaRNN

Benign

0.14

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;.;.;L;L;.;L

MutationTaster

Benign

0.99

D;D;D;D;D;D;D

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.28

N;.;.;.;N;N;N

REVEL

Benign

0.053

Sift

Benign

0.54

T;.;.;.;T;T;T

Sift4G

Benign

0.97

T;T;T;T;T;T;T

Polyphen

0.0010

B;.;B;B;B;B;B

Vest4

0.28

MutPred

0.40

.;.;.;Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);.;Loss of helix (P = 0.0104);

MVP

0.11

MPC

0.18

ClinPred

0.13

GERP RS

4.7

Varity_R

0.057

gMVP

0.32

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