chr7-99709134-C-T

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

Scores

3
10
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.61
Variant links:
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]

Genome browser will be placed here

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
CYP3A7NM_000765.5 linkuse as main transcriptc.1154G>A p.Gly385Glu missense_variant 11/13 ENST00000336374.4
CYP3A7-CYP3A51PNM_001256497.3 linkuse as main transcriptc.1154G>A p.Gly385Glu missense_variant 11/15

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CYP3A7ENST00000336374.4 linkuse as main transcriptc.1154G>A p.Gly385Glu missense_variant 11/131 NM_000765.5 P1P24462-1
CYP3A7ENST00000477357.5 linkuse as main transcriptn.1493G>A non_coding_transcript_exon_variant 8/102

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251266
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135798
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000545
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461726
Hom.:
0
Cov.:
32
AF XY:
0.00000550
AC XY:
4
AN XY:
727172
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
Cov.:
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 submitterclinical testingAmbry GeneticsMay 31, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.28
BayesDel_addAF
Benign
-0.033
T
BayesDel_noAF
Benign
-0.12
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.44
.;T;.
Eigen
Uncertain
0.31
Eigen_PC
Benign
0.11
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.96
D;D;D
MetaSVM
Uncertain
0.42
D
MutationAssessor
Uncertain
2.5
.;M;.
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.43
T
PROVEAN
Pathogenic
-7.3
.;D;.
REVEL
Pathogenic
0.68
Sift
Uncertain
0.018
.;D;.
Sift4G
Uncertain
0.0030
D;D;D
Polyphen
1.0
.;D;.
Vest4
0.53
MutPred
0.82
Loss of MoRF binding (P = 0.1079);Loss of MoRF binding (P = 0.1079);Loss of MoRF binding (P = 0.1079);
MVP
0.88
MPC
0.61
ClinPred
1.0
D
GERP RS
3.5
Varity_R
0.65
gMVP
0.90

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs375588438; hg19: chr7-99306757; COSMIC: COSV100312722; API