chr12-50144032-A-C

Position:

• chr12-50144032-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_147190.5(CERS5):​c.223T>G​(p.Cys75Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C75R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CERS5 NM_147190.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.541

Genes affected

CERS5 (HGNC:23749): (ceramide synthase 5) This gene encodes a protein that belongs to the TLC (TRAM, LAG1 and CLN8 homology domains) family of proteins. The encoded protein functions in the synthesis of ceramide, a lipid molecule that is involved in a several cellular signaling pathways. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045167714).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CERS5	NM_147190.5	c.223T>G	p.Cys75Gly	missense_variant	2/10	ENST00000317551.12	NP_671723.1
LOC124902931	XR_007063304.1	n.492+341A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CERS5	ENST00000317551.12	c.223T>G	p.Cys75Gly	missense_variant	2/10	2	NM_147190.5	ENSP00000325485	P1
	ENST00000548468.2	n.106-20994A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1459340 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726232

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: 0.00

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	0.063
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Benign	0.81
DEOGEN2	Benign	0.097	.;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.023	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.045	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.090	.;N;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.16	N;N;.
REVEL	Benign	0.12
Sift	Benign	0.36	T;T;.
Sift4G	Benign	0.37	T;T;.
Polyphen		0.0	.;B;.
Vest4		0.095
MutPred		0.47		.;Gain of catalytic residue at P71 (P = 0);Gain of catalytic residue at P71 (P = 0);
MVP		0.41
MPC		0.43
ClinPred		0.17	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.039
gMVP		0.26

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

Publications

LitVar

Other links and lift over

dbSNP: rs7302981; hg19: chr12-50537815;