Variant chr10-50813909-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014576.4(A1CF):c.1271C>T(p.Thr424Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,624 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 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: 9.60

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
A1CF	NM_014576.4 linkuse as main transcript	c.1271C>T	p.Thr424Ile	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.1271C>T	p.Thr424Ile	missense_variant	10/13	1	NM_014576.4	ENSP00000363109	A1	Q9NQ94-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152092

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461624

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727130

show subpopulations

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:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152092

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74282

Gnomad4 AFR

AF:

0.00

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Jul 25, 2023

The c.1319C>T (p.T440I) alteration is located in exon 12 (coding exon 8) of the A1CF gene. This alteration results from a C to T substitution at nucleotide position 1319, causing the threonine (T) at amino acid position 440 to be replaced by an isoleucine (I). 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.0022

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.22

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

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

.;D;D;D;D;.;.

M_CAP

Benign

0.037

MetaRNN

Uncertain

0.69

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

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

.;.;.;M;M;.;M

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-2.3

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

REVEL

Uncertain

0.30

Sift

Benign

0.091

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

Sift4G

Benign

0.12

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

Polyphen

0.95

P;.;P;D;D;P;D

Vest4

0.91

MutPred

0.43

.;.;.;Loss of loop (P = 0.0112);Loss of loop (P = 0.0112);.;Loss of loop (P = 0.0112);

MVP

0.33

MPC

0.85

ClinPred

0.92

GERP RS

5.0

Varity_R

0.19

gMVP

0.86

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