Variant 11-44048179-C-T 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.-448C>T 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 0.0000496 in 1,614,044 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: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000052 ( 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: -3.07

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=0.024574041).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACCSL	NM_001031854.2 link	c.143C>T	p.Thr48Met	missense_variant	Exon 1 of 14	ENST00000378832.1	NP_001027025.2	Q4AC99Q3C1W0
ACCSL	NM_001363113.1 link	c.-448C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 14		NP_001350042.1
ACCSL	XM_047426927.1 link	c.191C>T	p.Thr64Met	missense_variant	Exon 5 of 18		XP_047282883.1
ACCSL	NM_001363113.1 link	c.-448C>T		5_prime_UTR_variant	Exon 1 of 14		NP_001350042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACCSL	ENST00000378832.1 link	c.143C>T	p.Thr48Met	missense_variant	Exon 1 of 14	1	NM_001031854.2	ENSP00000368109.1		Q4AC99
ACCSL	ENST00000527145.1 link	n.143C>T		non_coding_transcript_exon_variant	Exon 1 of 14	1		ENSP00000436505.1		E9PI59

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000362

AC:

AN:

248928

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

135078

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.000278

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000520

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.0000536

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.0000468

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000413

AC:

Asia WGS

AF:

0.000289

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

Nov 11, 2024

The c.143C>T (p.T48M) alteration is located in exon 1 (coding exon 1) of the ACCSL gene. This alteration results from a C to T substitution at nucleotide position 143, causing the threonine (T) at amino acid position 48 to be replaced by a methionine (M). 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

0.085

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.0020

DANN

Benign

0.66

DEOGEN2

Benign

0.023

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0095

LIST_S2

Benign

0.39

M_CAP

Benign

0.012

MetaRNN

Benign

0.025

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.63

REVEL

Benign

0.051

Sift

Benign

0.28

Sift4G

Benign

0.25

Polyphen

0.0070

Vest4

0.057

MutPred

0.30

Gain of helix (P = 0.0022);

MVP

0.048

MPC

0.12

ClinPred

0.032

GERP RS

-7.7

Varity_R

0.013

gMVP

0.070

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