rs760743744

Variant names:

• chr2-168765662-C-G
• rs760743744
• NM_203463.3:c.916C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-168765662-C-G
• chr2-168765662-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_203463.3(CERS6):​c.916C>G​(p.Leu306Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: CERS6 NM_203463.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.758

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10688624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERS6	NM_203463.3	c.916C>G	p.Leu306Val	missense_variant	Exon 9 of 10	ENST00000305747.11	NP_982288.1
CERS6	NM_001256126.2	c.916C>G	p.Leu306Val	missense_variant	Exon 9 of 11		NP_001243055.1
CERS6	XM_017003749.3	c.493C>G	p.Leu165Val	missense_variant	Exon 6 of 8		XP_016859238.1
CERS6	XM_005246440.6	c.340C>G	p.Leu114Val	missense_variant	Exon 6 of 8		XP_005246497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERS6	ENST00000305747.11	c.916C>G	p.Leu306Val	missense_variant	Exon 9 of 10	2	NM_203463.3	ENSP00000306579.6
CERS6	ENST00000392687.4	c.916C>G	p.Leu306Val	missense_variant	Exon 9 of 11	1		ENSP00000376453.4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152158 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74332

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.22	T;.
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.068
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	0.055	N;N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.76	N;N
REVEL	Benign	0.23
Sift	Benign	1.0	T;T
Sift4G	Benign	0.70	T;T
Polyphen		0.0	B;.
Vest4		0.32
MutPred		0.58		Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.46
MPC		0.25
ClinPred		0.44	T
GERP RS		4.5
Varity_R		0.034
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs760743744; hg19: chr2-169622172;