rs369120327

Variant names:

• chr11-44050606-T-A
• rs369120327
• NM_001031854.2:c.619T>A

Your query was ambiguous. Multiple possible variants found:

• chr11-44050606-T-A
• chr11-44050606-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001031854.2(ACCSL):​c.619T>A​(p.Trp207Arg) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACCSL NM_001031854.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.934

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACCSL	NM_001031854.2	c.619T>A	p.Trp207Arg	missense_variant	Exon 3 of 14	ENST00000378832.1	NP_001027025.2
ACCSL	NM_001363113.1	c.76T>A	p.Trp26Arg	missense_variant	Exon 3 of 14		NP_001350042.1
ACCSL	XM_047426927.1	c.667T>A	p.Trp223Arg	missense_variant	Exon 7 of 18		XP_047282883.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACCSL	ENST00000378832.1	c.619T>A	p.Trp207Arg	missense_variant	Exon 3 of 14	1	NM_001031854.2	ENSP00000368109.1
ACCSL	ENST00000527145.1	n.*138T>A		non_coding_transcript_exon_variant	Exon 3 of 14	1		ENSP00000436505.1
ACCSL	ENST00000527145.1	n.*138T>A		3_prime_UTR_variant	Exon 3 of 14	1		ENSP00000436505.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000228 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Benign	0.86
DEOGEN2	Uncertain	0.60	D
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.045	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	-0.043	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-10	D
REVEL	Uncertain	0.33
Sift	Benign	0.037	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.53	P
Vest4		0.64
MutPred		0.78		Gain of disorder (P = 0.0033);
MVP		0.34
MPC		0.29
ClinPred		0.56	D
GERP RS		-0.20
Varity_R		0.18
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.25		Position offset: 16

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

Publications

LitVar

Other links and lift over

dbSNP: rs369120327; hg19: chr11-44072156;