11-44051355-G-C

Variant names:

• chr11-44051355-G-C
• rs371463744
• NM_001031854.2:c.656G>C

Variant summary

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

The NM_001031854.2(ACCSL):​c.656G>C​(p.Arg219Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R219Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ACCSL NM_001031854.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.656G>C	p.Arg219Pro	missense	Exon 4 of 14	NP_001027025.2	Q3C1W0
	ACCSL	NM_001363113.1		c.113G>C	p.Arg38Pro	missense	Exon 4 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.656G>C	p.Arg219Pro	missense	Exon 4 of 14	ENSP00000368109.1	Q4AC99
	ACCSL	ENST00000527145.1	TSL:1	n.*175G>C		non_coding_transcript_exon	Exon 4 of 14	ENSP00000436505.1	E9PI59
	ACCSL	ENST00000527145.1	TSL:1	n.*175G>C		3_prime_UTR	Exon 4 of 14	ENSP00000436505.1	E9PI59

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.71	D
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Uncertain	0.31	D
MutationAssessor	Pathogenic	2.9	M
PhyloP100		0.20
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-3.6	D
REVEL	Pathogenic	0.65
Sift	Benign	0.030	D
Sift4G	Uncertain	0.033	D
Polyphen		0.77	P
Vest4		0.71
MutPred		0.55		Gain of catalytic residue at R219 (P = 0.0565)
MVP		0.27
MPC		0.62
ClinPred		0.98	D
GERP RS		-0.10
Varity_R		0.86
gMVP		0.76
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs371463744; hg19: chr11-44072905;