NM_000106.6:c.1203G>C

Variant names:

• chr22-42126963-C-G
• rs28371732
• NM_000106.6:c.1203G>C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_000106.6(CYP2D6):​c.1203G>C​(p.Ser401Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,608,762 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S401S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00011 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0000069 (1 hom.)
• Consequence: CYP2D6 NM_000106.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -13.6
• Publications: 11 publications found

Genes affected

CYP2D6 (HGNC:2625): (cytochrome P450 family 2 subfamily D member 6) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is known to metabolize as many as 25% of commonly prescribed drugs. Its substrates include antidepressants, antipsychotics, analgesics and antitussives, beta adrenergic blocking agents, antiarrythmics and antiemetics. The gene is highly polymorphic in the human population; certain alleles result in the poor metabolizer phenotype, characterized by a decreased ability to metabolize the enzyme's substrates. Some individuals with the poor metabolizer phenotype have no functional protein since they carry 2 null alleles whereas in other individuals the gene is absent. This gene can vary in copy number and individuals with the ultrarapid metabolizer phenotype can have 3 or more active copies of the gene. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

NDUFA6-DT (HGNC:45273): (NDUFA6 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-13.6 with no splicing effect.
• BS2: High AC in GnomAd4 at 17 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000106.6. 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
	CYP2D6	NM_000106.6	MANE Select	c.1203G>C	p.Ser401Ser	synonymous	Exon 8 of 9	NP_000097.3
	CYP2D6	NM_001025161.3		c.1050G>C	p.Ser350Ser	synonymous	Exon 7 of 8	NP_001020332.2	P10635-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2D6	ENST00000645361.2	MANE Select	c.1203G>C	p.Ser401Ser	synonymous	Exon 8 of 9	ENSP00000496150.1	P10635-1
	CYP2D6	ENST00000359033.4	TSL:1	c.1050G>C	p.Ser350Ser	synonymous	Exon 7 of 8	ENSP00000351927.4	P10635-2
	CYP2D6	ENST00000360124.10	TSL:1	n.*278G>C		non_coding_transcript_exon	Exon 7 of 8	ENSP00000353241.6	H7BY38

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 151142 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000416

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

GnomAD2 exomes AF: 0.0000262 AC: 6 AN: 228710 AF XY: 0.0000243

Gnomad AFR exome AF: 0.000419

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000686 AC: 10 AN: 1457620 Hom.: 1 Cov.: 38 AF XY: 0.00000690 AC XY: 5 AN XY: 724866

African (AFR) AF: 0.000211 AC: 7 AN: 33250

American (AMR) AF: 0.00 AC: 0 AN: 44390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39522

South Asian (SAS) AF: 0.00 AC: 0 AN: 85622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1109488

Other (OTH) AF: 0.00 AC: 0 AN: 60182

GnomAD4 genome AF: 0.000112 AC: 17 AN: 151142 Hom.: 1 Cov.: 31 AF XY: 0.0000813 AC XY: 6 AN XY: 73784

African (AFR) AF: 0.000416 AC: 17 AN: 40860

American (AMR) AF: 0.00 AC: 0 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67780

Other (OTH) AF: 0.00 AC: 0 AN: 2070

Alfa AF: 0.00 Hom.: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.15
DANN	Benign	0.73
PhyloP100		-14
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs28371732; hg19: chr22-42522965;