15-51242798-A-T

Variant names:

• chr15-51242798-A-T
• rs2236722
• NM_000103.4:c.115T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_000103.4(CYP19A1):​c.115T>A​(p.Trp39Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CYP19A1 NM_000103.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.40
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 15-51242798-A-T is Benign according to our data. Variant chr15-51242798-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1606711.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP19A1	NM_000103.4	c.115T>A	p.Trp39Arg	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>A	p.Trp39Arg	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

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 21, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.77	D;D;D;.;T;.;.;.;T;T;T
Eigen	Benign	0.10
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.63	.;.;T;T;T;T;.;T;T;T;T
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.63	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Uncertain	2.2	M;M;M;.;.;.;M;M;.;.;.
PhyloP100		4.4
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-5.2	D;D;D;D;D;D;D;D;D;D;D
REVEL	Uncertain	0.36
Sift	Benign	0.033	D;D;D;T;D;D;D;D;D;D;D
Sift4G	Uncertain	0.055	T;T;T;T;.;T;T;T;T;T;.
Polyphen		0.34	B;B;B;.;.;.;.;.;.;.;.
Vest4		0.35
MutPred		0.27		Loss of catalytic residue at L37 (P = 0.0025);Loss of catalytic residue at L37 (P = 0.0025);Loss of catalytic residue at L37 (P = 0.0025);Loss of catalytic residue at L37 (P = 0.0025);Loss of catalytic residue at L37 (P = 0.0025);Loss of catalytic residue at L37 (P = 0.0025);Loss of catalytic residue at L37 (P = 0.0025);Loss of catalytic residue at L37 (P = 0.0025);Loss of catalytic residue at L37 (P = 0.0025);Loss of catalytic residue at L37 (P = 0.0025);Loss of catalytic residue at L37 (P = 0.0025);
MVP		0.96
MPC		0.23
ClinPred		0.99	D
GERP RS		5.5
PromoterAI		-0.0098	Neutral
Varity_R		0.70
gMVP		0.90
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2236722; hg19: chr15-51534995;