Variant chr10-50806872-C-G 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.1618G>C(p.Val540Leu) 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. 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

A1CF
NM_014576.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50

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=0.07813668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
A1CF	NM_014576.4 linkuse as main transcript	c.1618G>C	p.Val540Leu	missense_variant	13/13	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.1618G>C	p.Val540Leu	missense_variant	13/13	1	NM_014576.4	ENSP00000363109	A1	Q9NQ94-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000409

AC:

AN:

244642

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132070

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000552

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1455150

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723700

Gnomad4 AFR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Mar 22, 2022

The c.1666G>C (p.V556L) alteration is located in exon 15 (coding exon 11) of the A1CF gene. This alteration results from a G to C substitution at nucleotide position 1666, causing the valine (V) at amino acid position 556 to be replaced by a leucine (L). 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

0.10

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.080

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

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.83

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

M_CAP

Benign

0.0063

MetaRNN

Benign

0.078

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

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.34

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

MutationTaster

Benign

0.64

N;N;N;N;N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.15

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

REVEL

Benign

0.058

Sift

Benign

0.25

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

Sift4G

Benign

0.70

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

Polyphen

0.0

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

Vest4

0.031

MutPred

0.65

.;.;.;Gain of glycosylation at P549 (P = 0.146);Gain of glycosylation at P549 (P = 0.146);.;Gain of glycosylation at P549 (P = 0.146);

MVP

0.11

MPC

0.21

ClinPred

0.070

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.045

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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