rs2236722

Variant names:

• chr15-51242798-A-C
• NM_000103.4:c.115T>G

Your query was ambiguous. Multiple possible variants found:

• chr15-51242798-A-C
• chr15-51242798-A-G
• chr15-51242798-A-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_000103.4(CYP19A1):​c.115T>G​(p.Trp39Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W39R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CYP19A1 NM_000103.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.40

Genes affected

CYP19A1 (HGNC:2594): (cytochrome P450 family 19 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 endoplasmic reticulum and catalyzes the last steps of estrogen biosynthesis. Mutations in this gene can result in either increased or decreased aromatase activity; the associated phenotypes suggest that estrogen functions both as a sex steroid hormone and in growth or differentiation. Alternative promoter use and alternative splicing results in multiple transcript variants that have different tissue specificities. [provided by RefSeq, Dec 2016]

MIR4713HG (HGNC:53124): (MIR4713 host gene)

ACMG classification

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, 0.942

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.115T>G	p.Trp39Gly	missense_variant	Exon 2 of 10	ENST00000396402.6	NP_000094.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP19A1	ENST00000396402.6	c.115T>G	p.Trp39Gly	missense_variant	Exon 2 of 10	1	NM_000103.4	ENSP00000379683.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Pathogenic	0.80	D;D;D;.;T;.;.;.;T;T;T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.77	.;.;T;T;T;T;.;T;T;T;T
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.94	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.43	D
MutationAssessor	Uncertain	2.8	M;M;M;.;.;.;M;M;.;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-5.8	D;D;D;D;D;D;D;D;D;D;D
REVEL	Pathogenic	0.72
Sift	Uncertain	0.0010	D;D;D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.010	D;D;D;D;.;D;D;D;D;D;.
Polyphen		1.0	D;D;D;.;.;.;.;.;.;.;.
Vest4		0.67
MutPred		0.78		Loss of catalytic residue at L37 (P = 0.0081);Loss of catalytic residue at L37 (P = 0.0081);Loss of catalytic residue at L37 (P = 0.0081);Loss of catalytic residue at L37 (P = 0.0081);Loss of catalytic residue at L37 (P = 0.0081);Loss of catalytic residue at L37 (P = 0.0081);Loss of catalytic residue at L37 (P = 0.0081);Loss of catalytic residue at L37 (P = 0.0081);Loss of catalytic residue at L37 (P = 0.0081);Loss of catalytic residue at L37 (P = 0.0081);Loss of catalytic residue at L37 (P = 0.0081);
MVP		0.95
MPC		0.51
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.79
gMVP		0.82

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: chr15-51534995;