NM_203463.3:c.598A>T

Variant names:

• chr2-168695040-A-T
• NM_203463.3:c.598A>T

Variant summary

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

The NM_203463.3(CERS6):​c.598A>T​(p.Ile200Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,336 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CERS6 NM_203463.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.13

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 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
CERS6	NM_203463.3	c.598A>T	p.Ile200Phe	missense_variant	Exon 6 of 10	ENST00000305747.11	NP_982288.1
CERS6	NM_001256126.2	c.598A>T	p.Ile200Phe	missense_variant	Exon 6 of 11		NP_001243055.1
CERS6	XM_017003749.3	c.175A>T	p.Ile59Phe	missense_variant	Exon 3 of 8		XP_016859238.1
CERS6	XM_005246440.6	c.22A>T	p.Ile8Phe	missense_variant	Exon 3 of 8		XP_005246497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERS6	ENST00000305747.11	c.598A>T	p.Ile200Phe	missense_variant	Exon 6 of 10	2	NM_203463.3	ENSP00000306579.6
CERS6	ENST00000392687.4	c.598A>T	p.Ile200Phe	missense_variant	Exon 6 of 11	1		ENSP00000376453.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460336 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726570

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: 9.00e-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	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.78	D;.
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Uncertain	0.74	D
MutationAssessor	Pathogenic	3.5	M;M
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Pathogenic	0.77
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.98	D;.
Vest4		0.59
MutPred		0.51		Gain of ubiquitination at K203 (P = 0.0728);Gain of ubiquitination at K203 (P = 0.0728);
MVP		0.72
MPC		1.0
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.68
gMVP		0.66

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: chr2-169551550;