NM_001031854.2:c.599C>A

Variant names:

• chr11-44050586-C-A
• rs375824761
• NM_001031854.2:c.599C>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.599C>A​(p.Thr200Asn) 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. T200I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACCSL NM_001031854.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767
• 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=0.12214011).

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.599C>A	p.Thr200Asn	missense	Exon 3 of 14	NP_001027025.2	Q3C1W0
	ACCSL	NM_001363113.1		c.56C>A	p.Thr19Asn	missense	Exon 3 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.599C>A	p.Thr200Asn	missense	Exon 3 of 14	ENSP00000368109.1	Q4AC99
	ACCSL	ENST00000527145.1	TSL:1	n.*118C>A		non_coding_transcript_exon	Exon 3 of 14	ENSP00000436505.1	E9PI59
	ACCSL	ENST00000527145.1	TSL:1	n.*118C>A		3_prime_UTR	Exon 3 of 14	ENSP00000436505.1	E9PI59

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249420 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.0010
DANN	Benign	0.32
DEOGEN2	Benign	0.19	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.037	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	-0.97	N
PhyloP100		-0.77
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.20
Sift	Benign	0.47	T
Sift4G	Benign	0.48	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.68		Loss of phosphorylation at T200 (P = 0.1283)
MVP		0.048
MPC		0.14
ClinPred		0.048	T
GERP RS		-7.9
Varity_R		0.046
gMVP		0.23
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs375824761; hg19: chr11-44072136;