NM_183374.3:c.356A>C

Variant names:

• chr10-93062161-A-C
• rs201284617
• NM_183374.3:c.356A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_183374.3(CYP26C1):​c.356A>C​(p.Gln119Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00103 in 1,540,496 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q119E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00089 (12 hom.)
• Consequence: CYP26C1 NM_183374.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.81
• Publications: 5 publications found

Genes affected

CYP26C1 (HGNC:20577): (cytochrome P450 family 26 subfamily C member 1) 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 enzyme is involved in the catabolism of all-trans- and 9-cis-retinoic acid, and thus contributes to the regulation of retinoic acid levels in cells and tissues. This gene is adjacent to a related gene on chromosome 10q23.33. [provided by RefSeq, Jul 2008]

CYP26C1-DT (HGNC:55836): (CYP26C1 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012394369).
• BP6: Variant 10-93062161-A-C is Benign according to our data. Variant chr10-93062161-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 496733.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP26C1	NM_183374.3	c.356A>C	p.Gln119Pro	missense_variant	Exon 2 of 6	ENST00000651965.1	NP_899230.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP26C1	ENST00000651965.1	c.356A>C	p.Gln119Pro	missense_variant	Exon 2 of 6		NM_183374.3	ENSP00000498424.1
CYP26C1	ENST00000624358.3	n.356A>C		non_coding_transcript_exon_variant	Exon 2 of 6	2		ENSP00000485098.1
CYP26C1-DT	ENST00000847325.1	n.438T>G		non_coding_transcript_exon_variant	Exon 2 of 4
CYP26C1-DT	ENST00000847326.1	n.378T>G		non_coding_transcript_exon_variant	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.00227 AC: 345 AN: 152238 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0263

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00162 AC: 223 AN: 137874 AF XY: 0.00143

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00233

Gnomad FIN exome AF: 0.0227

Gnomad NFE exome AF: 0.000269

Gnomad OTH exome AF: 0.000719

GnomAD4 exome AF: 0.000893 AC: 1240 AN: 1388140 Hom.: 12 Cov.: 32 AF XY: 0.000850 AC XY: 582 AN XY: 685100

African (AFR) AF: 0.00 AC: 0 AN: 31584

American (AMR) AF: 0.00 AC: 0 AN: 35684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25138

East Asian (EAS) AF: 0.00459 AC: 164 AN: 35754

South Asian (SAS) AF: 0.000126 AC: 10 AN: 79172

European-Finnish (FIN) AF: 0.0204 AC: 789 AN: 38710

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5532

European-Non Finnish (NFE) AF: 0.000203 AC: 219 AN: 1078672

Other (OTH) AF: 0.00100 AC: 58 AN: 57894

GnomAD4 genome AF: 0.00226 AC: 345 AN: 152356 Hom.: 1 Cov.: 33 AF XY: 0.00319 AC XY: 238 AN XY: 74500

African (AFR) AF: 0.00 AC: 0 AN: 41592

American (AMR) AF: 0.00 AC: 0 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00425 AC: 22 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.0263 AC: 279 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000632 AC: 43 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00110 Hom.: 2

Bravo AF: 0.000295

ExAC AF: 0.000799 AC: 64

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Optic nerve hypoplasia Benign:1

-

Rare Disease Group, Clinical Genetics, Karolinska Institutet

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.8
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.40
Sift	Benign	0.18	T
Sift4G	Benign	0.11	T
Polyphen		0.96	D
Vest4		0.60
MVP		0.91
MPC		1.5
ClinPred		0.082	T
GERP RS		5.7
Varity_R		0.74
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs201284617; hg19: chr10-94821918;