chr7-99709134-C-T
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000765.5(CYP3A7):c.1154G>A(p.Gly385Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
CYP3A7
NM_000765.5 missense
NM_000765.5 missense
Scores
3
10
6
Clinical Significance
Conservation
PhyloP100: 5.61
Genes affected
CYP3A7 (HGNC:2640): (cytochrome P450 family 3 subfamily A member 7) This gene encodes a member of the cytochrome P450 superfamily of enzymes, which participate in drug metabolism and the synthesis of cholesterol, steroids and other lipids. This enzyme hydroxylates testosterone and dehydroepiandrosterone 3-sulphate, which is involved in the formation of estriol during pregnancy. This gene is part of a cluster of related genes on chromosome 7q21.1. Naturally-occurring readthrough transcription occurs between this gene and the downstream CYP3A51P pseudogene and is represented by GeneID:100861540. [provided by RefSeq, Jan 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.962
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP3A7 | NM_000765.5 | c.1154G>A | p.Gly385Glu | missense_variant | 11/13 | ENST00000336374.4 | |
CYP3A7-CYP3A51P | NM_001256497.3 | c.1154G>A | p.Gly385Glu | missense_variant | 11/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP3A7 | ENST00000336374.4 | c.1154G>A | p.Gly385Glu | missense_variant | 11/13 | 1 | NM_000765.5 | P1 | |
CYP3A7 | ENST00000477357.5 | n.1493G>A | non_coding_transcript_exon_variant | 8/10 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251266Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135798
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461726Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727172
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 31, 2023 | The c.1154G>A (p.G385E) alteration is located in exon 11 (coding exon 11) of the CYP3A7 gene. This alteration results from a G to A substitution at nucleotide position 1154, causing the glycine (G) at amino acid position 385 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
.;T;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
.;M;.
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Pathogenic
.;D;.
REVEL
Pathogenic
Sift
Uncertain
.;D;.
Sift4G
Uncertain
D;D;D
Polyphen
1.0
.;D;.
Vest4
MutPred
Loss of MoRF binding (P = 0.1079);Loss of MoRF binding (P = 0.1079);Loss of MoRF binding (P = 0.1079);
MVP
MPC
0.61
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at