chr1-47084743-A-T

Position:

• chr1-47084743-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_178134.3(CYP4Z1):​c.616A>T​(p.Ser206Cys) variant causes a missense, splice region 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. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 26)
• Consequence: CYP4Z1 NM_178134.3 missense, splice_region
• Scores: Splicing: ADA: 0.9991
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.405

Genes affected

CYP4Z1 (HGNC:20583): (cytochrome P450 family 4 subfamily Z 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 gene is part of a cluster of cytochrome P450 genes on chromosome 1p33. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP4Z1	NM_178134.3	c.616A>T	p.Ser206Cys	missense_variant, splice_region_variant	5/12	ENST00000334194.4	NP_835235.1
CYP4Z1	XM_024453856.2	c.502A>T	p.Ser168Cys	missense_variant, splice_region_variant	6/13		XP_024309624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP4Z1	ENST00000334194.4	c.616A>T	p.Ser206Cys	missense_variant, splice_region_variant	5/12	1	NM_178134.3	ENSP00000334246.3

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 26

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 02, 2023

The c.616A>T (p.S206C) alteration is located in exon 5 (coding exon 5) of the CYP4Z1 gene. This alteration results from a A to T substitution at nucleotide position 616, causing the serine (S) at amino acid position 206 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.072	T
Eigen	Benign	0.015
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.33
Sift	Benign	0.093	T
Sift4G	Uncertain	0.053	T
Polyphen		1.0	D
Vest4		0.28
MutPred		0.61		Loss of disorder (P = 0.0065);
MVP		0.35
MPC		1.6
ClinPred		0.63	D
GERP RS		1.8
Varity_R		0.18
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.98
SpliceAI score (max)		0.44		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.44		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-47550415;