chr5-131972810-C-A

Variant names:

• chr5-131972810-C-A
• NM_001009185.3:c.1252G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001009185.3(ACSL6):​c.1252G>T​(p.Ala418Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACSL6 NM_001009185.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.79
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.789

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009185.3. 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
	ACSL6	NM_001009185.3	MANE Select	c.1252G>T	p.Ala418Ser	missense	Exon 13 of 21	NP_001009185.1	Q9UKU0-1
	ACSL6	NM_015256.4		c.1252G>T	p.Ala418Ser	missense	Exon 13 of 21	NP_056071.2	Q9UKU0-8
	ACSL6	NM_001405475.1		c.1246G>T	p.Ala416Ser	missense	Exon 14 of 22	NP_001392404.1	A0A494C0B6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSL6	ENST00000651883.2	MANE Select	c.1252G>T	p.Ala418Ser	missense	Exon 13 of 21	ENSP00000499063.2	Q9UKU0-1
	ACSL6	ENST00000543479.5	TSL:1	c.1222G>T	p.Ala408Ser	missense	Exon 13 of 21	ENSP00000442124.2	Q9UKU0-6
	ACSL6	ENST00000379246.5	TSL:1	c.1210G>T	p.Ala404Ser	missense	Exon 13 of 21	ENSP00000368548.1	Q9UKU0-9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.045	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Uncertain	-0.035	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		7.8
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.016	D
Polyphen		1.0	D
Vest4		0.47
MutPred		0.67		Gain of disorder (P = 0.0464)
MVP		0.86
MPC		0.74
ClinPred		0.97	D
GERP RS		6.0
Varity_R		0.40
gMVP		0.55
Mutation Taster		=84/16	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

hg19: chr5-131308503;