dbSNP rs771988532: CERS6:p.Leu143Ile (chr2-168631004-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.39

Variant links:

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]

CERS6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 link	c.427C>A	p.Leu143Ile	missense_variant	Exon 4 of 10	ENST00000305747.11	NP_982288.1	Q6ZMG9-1
CERS6	NM_001256126.2 link	c.427C>A	p.Leu143Ile	missense_variant	Exon 4 of 11		NP_001243055.1	Q6ZMG9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERS6	ENST00000305747.11 link	c.427C>A	p.Leu143Ile	missense_variant	Exon 4 of 10	2	NM_203463.3	ENSP00000306579.6		Q6ZMG9-1
CERS6	ENST00000392687.4 link	c.427C>A	p.Leu143Ile	missense_variant	Exon 4 of 11	1		ENSP00000376453.4		Q6ZMG9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.28e-7

AC:

AN:

1373158

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

685274

show subpopulations

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.:

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

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.33

T;.

Eigen

Benign

0.12

Eigen_PC

Benign

0.041

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.070

MetaRNN

Benign

0.42

T;T

MetaSVM

Uncertain

0.19

MutationAssessor

Uncertain

2.5

M;M

PrimateAI

Uncertain

0.50

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over