Genetic Variant ACCSL:p.Ser148Leu (chr11-44048479-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001363113.1(ACCSL):c.-148C>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 0.0000211 in 1,609,498 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 0.000054 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000018 ( 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: -0.430

Publications

3 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06534952).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363113.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACCSL	NM_001031854.2	MANE Select	c.443C>T	p.Ser148Leu	missense	Exon 1 of 14	NP_001027025.2	Q3C1W0
ACCSL	NM_001363113.1		c.-148C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	NP_001350042.1
ACCSL	NM_001363113.1		c.-148C>T		5_prime_UTR	Exon 1 of 14	NP_001350042.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACCSL	ENST00000378832.1	TSL:1 MANE Select	c.443C>T	p.Ser148Leu	missense	Exon 1 of 14	ENSP00000368109.1	Q4AC99
	ACCSL	ENST00000527145.1	TSL:1	n.443C>T		non_coding_transcript_exon	Exon 1 of 14	ENSP00000436505.1	E9PI59

Frequencies

GnomAD3 genomes

AF:

0.0000541

AC:

AN:

147880

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000151

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:

0.0000148

Gnomad OTH

AF:

0.000492

GnomAD2 exomes

AF:

0.0000281

AC:

AN:

249100

AF XY:

0.0000444

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1461618

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727124

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53218

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

1111984

Other (OTH)

AF:

0.0000166

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000541

AC:

AN:

147880

Hom.:

Cov.:

AF XY:

0.0000837

AC XY:

AN XY:

71670

show subpopulations

African (AFR)

AF:

0.000151

AC:

AN:

39838

American (AMR)

AF:

0.00

AC:

AN:

14236

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5014

South Asian (SAS)

AF:

0.00

AC:

AN:

4710

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9726

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67662

Other (OTH)

AF:

0.000492

AC:

AN:

2032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.54

CADD

Benign

4.9

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.043

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0098

LIST_S2

Benign

0.59

M_CAP

Benign

0.018

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.58

PhyloP100

-0.43

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.2

REVEL

Benign

0.066

Sift

Benign

0.39

Sift4G

Benign

0.41

Polyphen

0.0050

Vest4

0.083

MutPred

0.47

Gain of catalytic residue at S148 (P = 0.0345)

MVP

0.13

MPC

0.11

ClinPred

0.020

GERP RS

-1.7

PromoterAI

-0.0086

Neutral

(source)

Varity_R

0.040

gMVP

0.21

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over