2-168631004-C-A

Variant names:

• chr2-168631004-C-A
• NM_203463.3:c.427C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_203463.3(CERS6):​c.427C>A​(p.Leu143Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000728 in 1,373,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: CERS6 NM_203463.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.39

Genes affected

CERS6 (HGNC:23826): (ceramide synthase 6) Enables sphingosine N-acyltransferase activity. Involved in ceramide biosynthetic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42029673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERS6	NM_203463.3	c.427C>A	p.Leu143Ile	missense_variant	Exon 4 of 10	ENST00000305747.11	NP_982288.1
CERS6	NM_001256126.2	c.427C>A	p.Leu143Ile	missense_variant	Exon 4 of 11		NP_001243055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERS6	ENST00000305747.11	c.427C>A	p.Leu143Ile	missense_variant	Exon 4 of 10	2	NM_203463.3	ENSP00000306579.6
CERS6	ENST00000392687.4	c.427C>A	p.Leu143Ile	missense_variant	Exon 4 of 11	1		ENSP00000376453.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.28e-7 AC: 1 AN: 1373158 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 685274

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: 9.51e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.33	T;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.041
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.42	T;T
MetaSVM	Uncertain	0.19	D
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.99	N;N
REVEL	Uncertain	0.52
Sift	Benign	0.21	T;T
Sift4G	Uncertain	0.057	T;T
Polyphen		0.81	P;.
Vest4		0.43
MutPred		0.71		Gain of MoRF binding (P = 0.1053);Gain of MoRF binding (P = 0.1053);
MVP		0.49
MPC		0.26
ClinPred		0.55	D
GERP RS		3.6
Varity_R		0.21
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr2-169487514;