chr15-100402839-G-A

Variant names:

• chr15-100402839-G-A
• rs116101674
• NM_001378789.1:c.1026C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001378789.1(CERS3):​c.1026C>T​(p.Asp342Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00517 in 1,608,880 control chromosomes in the GnomAD database, including 168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0086 (24 hom., cov: 33)
  • Exomes 𝑓: 0.0048 (144 hom.)
• Consequence: CERS3 NM_001378789.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.535
• Publications: 3 publications found

Genes affected

CERS3 (HGNC:23752): (ceramide synthase 3) This gene is a member of the ceramide synthase family of genes. The ceramide synthase enzymes regulate sphingolipid synthesis by catalyzing the formation of ceramides from sphingoid base and acyl-coA substrates. This family member is involved in the synthesis of ceramides with ultra-long-chain acyl moieties (ULC-Cers), important to the epidermis in its role in creating a protective barrier from the environment. The protein encoded by this gene has also been implicated in modification of the lipid structures required for spermatogenesis. Mutations in this gene have been associated with male fertility defects, and epidermal defects, including ichthyosis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

CERS3-AS1 (HGNC:51431): (CERS3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-100402839-G-A is Benign according to our data. Variant chr15-100402839-G-A is described in ClinVar as Benign. ClinVar VariationId is 2018095.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.535 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0595 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378789.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERS3	NM_001378789.1	MANE Select	c.1026C>T	p.Asp342Asp	synonymous	Exon 12 of 12	NP_001365718.1	Q8IU89
	CERS3	NM_001290341.2		c.1059C>T	p.Asp353Asp	synonymous	Exon 14 of 14	NP_001277270.1	Q8IU89
	CERS3	NM_001290342.2		c.1026C>T	p.Asp342Asp	synonymous	Exon 13 of 13	NP_001277271.1	Q8IU89

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERS3	ENST00000679737.1	MANE Select	c.1026C>T	p.Asp342Asp	synonymous	Exon 12 of 12	ENSP00000506641.1	Q8IU89
	CERS3	ENST00000284382.8	TSL:1	c.1026C>T	p.Asp342Asp	synonymous	Exon 13 of 13	ENSP00000284382.4	Q8IU89
	CERS3	ENST00000394113.5	TSL:1	c.1026C>T	p.Asp342Asp	synonymous	Exon 14 of 14	ENSP00000377672.3	Q8IU89

Frequencies

GnomAD3 genomes AF: 0.00850 AC: 1292 AN: 152020 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.00578

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0492

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.00926

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00163

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.0134 AC: 3210 AN: 239514 AF XY: 0.0123

Gnomad AFR exome AF: 0.00607

Gnomad AMR exome AF: 0.0620

Gnomad ASJ exome AF: 0.000713

Gnomad EAS exome AF: 0.00756

Gnomad FIN exome AF: 0.0000962

Gnomad NFE exome AF: 0.00161

Gnomad OTH exome AF: 0.0147

GnomAD4 exome AF: 0.00481 AC: 7012 AN: 1456742 Hom.: 144 Cov.: 33 AF XY: 0.00510 AC XY: 3697 AN XY: 724254

African (AFR) AF: 0.00545 AC: 182 AN: 33418

American (AMR) AF: 0.0614 AC: 2690 AN: 43808

Ashkenazi Jewish (ASJ) AF: 0.000538 AC: 14 AN: 26010

East Asian (EAS) AF: 0.00871 AC: 345 AN: 39598

South Asian (SAS) AF: 0.0221 AC: 1893 AN: 85516

European-Finnish (FIN) AF: 0.000169 AC: 9 AN: 53162

Middle Eastern (MID) AF: 0.0125 AC: 72 AN: 5764

European-Non Finnish (NFE) AF: 0.00127 AC: 1408 AN: 1109242

Other (OTH) AF: 0.00663 AC: 399 AN: 60224

GnomAD4 genome AF: 0.00862 AC: 1312 AN: 152138 Hom.: 24 Cov.: 33 AF XY: 0.00949 AC XY: 706 AN XY: 74376

African (AFR) AF: 0.00581 AC: 241 AN: 41488

American (AMR) AF: 0.0499 AC: 763 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000866 AC: 3 AN: 3464

East Asian (EAS) AF: 0.00928 AC: 48 AN: 5172

South Asian (SAS) AF: 0.0230 AC: 111 AN: 4820

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10572

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00163 AC: 111 AN: 68014

Other (OTH) AF: 0.0132 AC: 28 AN: 2114

Alfa AF: 0.00323 Hom.: 0

Bravo AF: 0.0109

Asia WGS AF: 0.0290 AC: 100 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.43
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs116101674; hg19: chr15-100943044;