1-46934197-C-T

Position:

• chr1-46934197-C-T

Variant summary

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

The NM_000778.4(CYP4A11):​c.1067G>A​(p.Gly356Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: CYP4A11 NM_000778.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.41

Genes affected

CYP4A11 (HGNC:2642): (cytochrome P450 family 4 subfamily A member 11) 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 hydroxylates medium-chain fatty acids such as laurate and myristate. Multiple transcript variants have been found for this gene. [provided by RefSeq, Jan 2016]

CYP4A11 (HGNC:):

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
CYP4A11	NM_000778.4	c.1067G>A	p.Gly356Asp	missense_variant	8/12	ENST00000310638.9	NP_000769.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP4A11	ENST00000310638.9	c.1067G>A	p.Gly356Asp	missense_variant	8/12	1	NM_000778.4	ENSP00000311095.4
CYP4A11	ENST00000465874.5	n.609-192G>A		intron_variant		2		ENSP00000476368.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 29

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

Sep 06, 2022

The c.1067G>A (p.G356D) alteration is located in exon 8 (coding exon 8) of the CYP4A11 gene. This alteration results from a G to A substitution at nucleotide position 1067, causing the glycine (G) at amino acid position 356 to be replaced by an aspartic acid (D). 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	0.21
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	D;.;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.15	N
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.63	D;D;D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Pathogenic	3.1	M;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-6.3	D;D;D
REVEL	Uncertain	0.39
Sift	Benign	0.060	T;T;D
Sift4G	Benign	0.14	T;T;T
Polyphen		1.0	D;.;.
Vest4		0.27
MutPred		0.69		Gain of solvent accessibility (P = 0.1014);.;Gain of solvent accessibility (P = 0.1014);
MVP		0.82
MPC		0.40
ClinPred		0.99	D
GERP RS		4.3
Varity_R		0.58
gMVP		0.49

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-47399869;