NM_000781.3:c.940G>C

Variant names:

• chr15-74343027-C-G
• NM_000781.3:c.940G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000781.3(CYP11A1):​c.940G>C​(p.Glu314Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CYP11A1 NM_000781.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95

Genes affected

CYP11A1 (HGNC:2590): (cytochrome P450 family 11 subfamily A 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 protein localizes to the mitochondrial inner membrane and catalyzes the conversion of cholesterol to pregnenolone, the first and rate-limiting step in the synthesis of the steroid hormones. Two transcript variants encoding different isoforms have been found for this gene. The cellular location of the smaller isoform is unclear since it lacks the mitochondrial-targeting transit peptide. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29673648).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP11A1	NM_000781.3	c.940G>C	p.Glu314Gln	missense_variant	Exon 5 of 9	ENST00000268053.11	NP_000772.2
CYP11A1	NM_001099773.2	c.466G>C	p.Glu156Gln	missense_variant	Exon 5 of 9		NP_001093243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP11A1	ENST00000268053.11	c.940G>C	p.Glu314Gln	missense_variant	Exon 5 of 9	1	NM_000781.3	ENSP00000268053.6
CYP11A1	ENST00000358632.8	c.466G>C	p.Glu156Gln	missense_variant	Exon 5 of 9	2		ENSP00000351455.4
CYP11A1	ENST00000566674.5	c.466G>C	p.Glu156Gln	missense_variant	Exon 5 of 6	5		ENSP00000456941.1
CYP11A1	ENST00000435365.5	n.940G>C		non_coding_transcript_exon_variant	Exon 5 of 8	3		ENSP00000391081.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460802 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726722

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.44	.;T;.
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.79	T;T;T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.6	.;L;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.030	D;D;D
Sift4G	Uncertain	0.027	D;D;.
Polyphen		0.33	.;B;.
Vest4		0.10
MutPred		0.38		.;Gain of ubiquitination at K310 (P = 0.102);.;
MVP		0.86
MPC		0.45
ClinPred		0.81	D
GERP RS		1.4
Varity_R		0.48
gMVP		0.45

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: chr15-74635368;