Variant chr19-2249584-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000479.5(AMH):c.252G>A(p.Leu84=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 1,566,996 control chromosomes in the GnomAD database, including 1,857 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 164 hom., cov: 33)

Exomes 𝑓: 0.044 ( 1693 hom. )

Consequence

AMH
NM_000479.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.00

Variant links:

Genes affected

AMH (HGNC:464): (anti-Mullerian hormone) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate N- and C-terminal cleavage products that homodimerize and associate to form a biologically active noncovalent complex. This complex binds to the anti-Mullerian hormone receptor type 2 and causes the regression of Mullerian ducts in the male embryo that would otherwise differentiate into the uterus and fallopian tubes. This protein also plays a role in Leydig cell differentiation and function and follicular development in adult females. Mutations in this gene result in persistent Mullerian duct syndrome. [provided by RefSeq, Jul 2016]

AMH links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 19-2249584-G-A is Benign according to our data. Variant chr19-2249584-G-A is described in ClinVar as [Benign]. Clinvar id is 1237409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-2249584-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMH	NM_000479.5 linkuse as main transcript	c.252G>A	p.Leu84=	synonymous_variant	1/5	ENST00000221496.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMH	ENST00000221496.5 linkuse as main transcript	c.252G>A	p.Leu84=	synonymous_variant	1/5	1	NM_000479.5	P1
AMH	ENST00000592877.1 linkuse as main transcript	n.276G>A		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.0361

AC:

5497

AN:

152206

Hom.:

164

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00890

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0364

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.0846

Gnomad FIN

AF:

0.0638

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0386

Gnomad OTH

AF:

0.0334

GnomAD3 exomes

AF:

0.0571

AC:

10002

AN:

175188

Hom.:

400

AF XY:

0.0582

AC XY:

5597

AN XY:

96118

show subpopulations

Gnomad AFR exome

AF:

0.00658

Gnomad AMR exome

AF:

0.0563

Gnomad ASJ exome

AF:

0.0226

Gnomad EAS exome

AF:

0.150

Gnomad SAS exome

AF:

0.0799

Gnomad FIN exome

AF:

0.0773

Gnomad NFE exome

AF:

0.0406

Gnomad OTH exome

AF:

0.0480

GnomAD4 exome

AF:

0.0436

AC:

61735

AN:

1414672

Hom.:

1693

Cov.:

AF XY:

0.0448

AC XY:

31344

AN XY:

700294

show subpopulations

Gnomad4 AFR exome

AF:

0.00609

Gnomad4 AMR exome

AF:

0.0525

Gnomad4 ASJ exome

AF:

0.0203

Gnomad4 EAS exome

AF:

0.105

Gnomad4 SAS exome

AF:

0.0819

Gnomad4 FIN exome

AF:

0.0727

Gnomad4 NFE exome

AF:

0.0389

Gnomad4 OTH exome

AF:

0.0440

GnomAD4 genome

AF:

0.0360

AC:

5490

AN:

152324

Hom.:

164

Cov.:

AF XY:

0.0382

AC XY:

2849

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00887

Gnomad4 AMR

AF:

0.0364

Gnomad4 ASJ

AF:

0.0173

Gnomad4 EAS

AF:

0.129

Gnomad4 SAS

AF:

0.0843

Gnomad4 FIN

AF:

0.0638

Gnomad4 NFE

AF:

0.0386

Gnomad4 OTH

AF:

0.0331

Alfa

AF:

0.0265

Hom.:

Bravo

AF:

0.0336

Asia WGS

AF:

0.0900

AC:

312

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

2.6

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over