rs547078642

Variant names:

• chr4-84635283-A-T
• rs547078642
• NM_001263.4:c.742A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001263.4(CDS1):​c.742A>T​(p.Ser248Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000224 in 1,564,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: CDS1 NM_001263.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.26
• Publications: 0 publications found

Genes affected

CDS1 (HGNC:1800): (CDP-diacylglycerol synthase 1) Breakdown products of phosphoinositides are ubiquitous second messengers that function downstream of many G protein-coupled receptors and tyrosine kinases regulating cell growth, calcium metabolism, and protein kinase C activity. This gene encodes an enzyme which regulates the amount of phosphatidylinositol available for signaling by catalyzing the conversion of phosphatidic acid to CDP-diacylglycerol. This enzyme is an integral membrane protein localized to two subcellular domains, the matrix side of the inner mitochondrial membrane where it is thought to be involved in the synthesis of phosphatidylglycerol and cardiolipin and the cytoplasmic side of the endoplasmic reticulum where it functions in phosphatidylinositol biosynthesis. Two genes encoding this enzyme have been identified in humans, one mapping to human chromosome 4q21 and a second to 20p13. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12900963).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001263.4. 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
	CDS1	NM_001263.4	MANE Select	c.742A>T	p.Ser248Cys	missense	Exon 8 of 13	NP_001254.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDS1	ENST00000295887.6	TSL:1 MANE Select	c.742A>T	p.Ser248Cys	missense	Exon 8 of 13	ENSP00000295887.5	Q92903
	CDS1	ENST00000891571.1		c.838A>T	p.Ser280Cys	missense	Exon 8 of 13	ENSP00000561630.1
	CDS1	ENST00000959938.1		c.838A>T	p.Ser280Cys	missense	Exon 8 of 12	ENSP00000629997.1

Frequencies

GnomAD3 genomes AF: 0.0000199 AC: 3 AN: 150896 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000660

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: 0.0000295

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000219 AC: 5 AN: 228226 AF XY: 0.0000324

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000372

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000226 AC: 32 AN: 1413364 Hom.: 0 Cov.: 26 AF XY: 0.0000213 AC XY: 15 AN XY: 704366

African (AFR) AF: 0.0000320 AC: 1 AN: 31208

American (AMR) AF: 0.0000260 AC: 1 AN: 38428

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25450

East Asian (EAS) AF: 0.00 AC: 0 AN: 39260

South Asian (SAS) AF: 0.00 AC: 0 AN: 80420

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49562

Middle Eastern (MID) AF: 0.000710 AC: 4 AN: 5630

European-Non Finnish (NFE) AF: 0.0000221 AC: 24 AN: 1084796

Other (OTH) AF: 0.0000341 AC: 2 AN: 58610

GnomAD4 genome AF: 0.0000199 AC: 3 AN: 151008 Hom.: 0 Cov.: 31 AF XY: 0.0000407 AC XY: 3 AN XY: 73676

African (AFR) AF: 0.00 AC: 0 AN: 41100

American (AMR) AF: 0.0000659 AC: 1 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5134

South Asian (SAS) AF: 0.00 AC: 0 AN: 4748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67822

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000480 Hom.: 0

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Benign	0.88
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.26
Eigen_PC	Benign	0.023
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.81	N
PhyloP100		5.3
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	0.71	N
REVEL	Benign	0.099
Sift	Benign	0.25	T
Sift4G	Benign	0.25	T
Polyphen		0.0010	B
Vest4		0.38
MVP		0.45
MPC		0.26
ClinPred		0.15	T
GERP RS		5.7
Varity_R		0.19
gMVP		0.75
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs547078642; hg19: chr4-85556436;