11-44048368-C-A

Variant names:

• chr11-44048368-C-A
• rs1952613917
• NM_001031854.2:c.332C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001031854.2(ACCSL):​c.332C>A​(p.Ala111Asp) 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A111V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ACCSL NM_001031854.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07959777).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031854.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACCSL	NM_001031854.2	MANE Select	c.332C>A	p.Ala111Asp	missense	Exon 1 of 14	NP_001027025.2	Q3C1W0
	ACCSL	NM_001363113.1		c.-259C>A		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.332C>A	p.Ala111Asp	missense	Exon 1 of 14	ENSP00000368109.1	Q4AC99
	ACCSL	ENST00000527145.1	TSL:1	n.332C>A		non_coding_transcript_exon	Exon 1 of 14	ENSP00000436505.1	E9PI59

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	2.7
DANN	Benign	0.84
DEOGEN2	Benign	0.042	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.048
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.19
Sift	Benign	0.27	T
Sift4G	Benign	0.59	T
Polyphen		0.20	B
Vest4		0.14
MutPred		0.20		Loss of helix (P = 0.0068)
MVP		0.092
MPC		0.39
ClinPred		0.11	T
GERP RS		-0.53
PromoterAI		-0.096	Neutral
Varity_R		0.069
gMVP		0.16
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs1952613917; hg19: chr11-44069918;