rs267606654

chr19-2251418-G-Achr19-2251418-G-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_000479.5(AMH):c.1144G>A(p.Glu382Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AMH NM_000479.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.860

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]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.40534794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMH	NM_000479.5	c.1144G>A	p.Glu382Lys	missense_variant	5/5	ENST00000221496.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMH	ENST00000221496.5	c.1144G>A	p.Glu382Lys	missense_variant	5/5	1	NM_000479.5	P1
AMH	ENST00000589313.2	n.1497G>A		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1293046 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 637004

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
Cadd	Benign	17
Dann	Benign	0.89
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.62	T
M_CAP	Pathogenic	0.99	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	0.99	N
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	0.54	N
REVEL	Benign	0.27
Sift	Benign	1.0	T
Sift4G	Benign	0.49	T
Polyphen		0.56	P
Vest4		0.14
MutPred		0.58		Gain of MoRF binding (P = 0.002);
MVP		0.81
MPC		2.1
ClinPred		0.19	T
GERP RS		3.0
Varity_R		0.097
gMVP		0.44

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

Other links and lift over

dbSNP: rs267606654; hg19: chr19-2251417;