Variant 11-44048413-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001363113.1(ACCSL):c.-214G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ACCSL
NM_001363113.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.78

Variant links:

Genes affected

ACCSL (HGNC:34391): (1-aminocyclopropane-1-carboxylate synthase homolog (inactive) like) Predicted to enable catalytic activity and pyridoxal phosphate binding activity. Predicted to be involved in biosynthetic process. [provided by Alliance of Genome Resources, Apr 2022]

ACCSL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.044704735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACCSL	NM_001031854.2 link	c.377G>A	p.Cys126Tyr	missense_variant	1/14	ENST00000378832.1	NP_001027025.2	Q4AC99Q3C1W0
ACCSL	NM_001363113.1 link	c.-214G>A		5_prime_UTR_premature_start_codon_gain_variant	1/14		NP_001350042.1
ACCSL	XM_047426927.1 link	c.425G>A	p.Cys142Tyr	missense_variant	5/18		XP_047282883.1
ACCSL	NM_001363113.1 link	c.-214G>A		5_prime_UTR_variant	1/14		NP_001350042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACCSL	ENST00000378832.1 link	c.377G>A	p.Cys126Tyr	missense_variant	1/14	1	NM_001031854.2	ENSP00000368109.1		Q4AC99
ACCSL	ENST00000527145.1 link	n.377G>A		non_coding_transcript_exon_variant	1/14	1		ENSP00000436505.1		E9PI59

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249428

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135324

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

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

AF:

0.00000137

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

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.:

ExAC

AF:

0.00000827

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

Sep 24, 2024

The c.377G>A (p.C126Y) alteration is located in exon 1 (coding exon 1) of the ACCSL gene. This alteration results from a G to A substitution at nucleotide position 377, causing the cysteine (C) at amino acid position 126 to be replaced by a tyrosine (Y). 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

0.066

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.0030

DANN

Benign

0.36

DEOGEN2

Benign

0.015

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.32

M_CAP

Benign

0.023

MetaRNN

Benign

0.045

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.90

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.60

REVEL

Benign

0.072

Sift

Benign

0.55

Sift4G

Benign

1.0

Polyphen

0.056

Vest4

0.072

MutPred

0.39

Gain of phosphorylation at C126 (P = 0.0325);

MVP

0.040

MPC

0.22

ClinPred

0.024

GERP RS

-6.2

Varity_R

0.028

gMVP

0.085

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