rs762139509

Variant names:

• chr5-131972782-C-G
• NM_001009185.3:c.1280G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-131972782-C-G
• chr5-131972782-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001009185.3(ACSL6):​c.1280G>C​(p.Arg427Pro) 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 1,461,890 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. R427Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ACSL6 NM_001009185.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23

Genes affected

ACSL6 (HGNC:16496): (acyl-CoA synthetase long chain family member 6) The protein encoded by this gene catalyzes the formation of acyl-CoA from fatty acids, ATP, and CoA, using magnesium as a cofactor. The encoded protein plays a major role in fatty acid metabolism in the brain. Translocations with the ETV6 gene are causes of myelodysplastic syndrome with basophilia, acute myelogenous leukemia with eosinophilia, and acute eosinophilic leukemia. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Apr 2011]

ENSG00000281938 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSL6	NM_001009185.3	c.1280G>C	p.Arg427Pro	missense_variant	Exon 13 of 21	ENST00000651883.2	NP_001009185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSL6	ENST00000651883.2	c.1280G>C	p.Arg427Pro	missense_variant	Exon 13 of 21		NM_001009185.3	ENSP00000499063.2
ENSG00000281938	ENST00000652469.1	n.1280G>C		non_coding_transcript_exon_variant	Exon 13 of 26			ENSP00000498837.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727246

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	.;.;.;.;.;.;T;.;.
Eigen	Benign	0.0038
Eigen_PC	Benign	-0.023
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	D;D;.;D;D;D;D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.51	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;.;.;.;.;M;M;.;.
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.6	D;D;D;D;D;D;D;.;D
REVEL	Benign	0.20
Sift	Uncertain	0.0070	D;D;D;D;D;D;D;.;D
Sift4G	Benign	0.14	T;T;T;T;T;T;T;T;T
Polyphen		0.83	P;P;P;P;.;B;B;P;.
Vest4		0.36
MutPred		0.62		.;.;.;.;.;Loss of MoRF binding (P = 0.0099);Loss of MoRF binding (P = 0.0099);.;.;
MVP		0.55
MPC		0.91
ClinPred		0.98	D
GERP RS		3.3
Varity_R		0.80
gMVP		0.78

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-131308475;