11-44048497-A-G

Variant names:

• chr11-44048497-A-G
• rs1952615243
• NM_001031854.2:c.461A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001031854.2(ACCSL):​c.461A>G​(p.Asn154Ser) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACCSL NM_001031854.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00300

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]

ACMG classification

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=0.030122042).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACCSL	NM_001031854.2	c.461A>G	p.Asn154Ser	missense_variant	Exon 1 of 14	ENST00000378832.1	NP_001027025.2
ACCSL	XM_047426927.1	c.509A>G	p.Asn170Ser	missense_variant	Exon 5 of 18		XP_047282883.1
ACCSL	NM_001363113.1	c.-130A>G		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	c.461A>G	p.Asn154Ser	missense_variant	Exon 1 of 14	1	NM_001031854.2	ENSP00000368109.1
ACCSL	ENST00000527145.1	n.461A>G		non_coding_transcript_exon_variant	Exon 1 of 14	1		ENSP00000436505.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000138 AC: 2 AN: 1444682 Hom.: 1 Cov.: 32 AF XY: 0.00000278 AC XY: 2 AN XY: 718710

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: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.461A>G (p.N154S) alteration is located in exon 1 (coding exon 1) of the ACCSL gene. This alteration results from a A to G substitution at nucleotide position 461, causing the asparagine (N) at amino acid position 154 to be replaced by a serine (S). 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	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.8
DANN	Benign	0.38
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.90	L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.086
Sift	Benign	0.53	T
Sift4G	Benign	0.47	T
Polyphen		0.016	B
Vest4		0.093
MutPred		0.30		Loss of loop (P = 0.0374);
MVP		0.13
MPC		0.11
ClinPred		0.048	T
GERP RS		-1.7
Varity_R		0.022
gMVP		0.081

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

Other links and lift over

dbSNP: rs1952615243; hg19: chr11-44070047;