rs11170553

Variant names:

• chr12-53428308-C-T
• rs11170553
• NM_020547.3:c.853-588C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020547.3(AMHR2):​c.853-588C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0464 in 152,298 control chromosomes in the GnomAD database, including 214 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.046 (214 hom., cov: 32)
• Consequence: AMHR2 NM_020547.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900
• Publications: 3 publications found

Genes affected

AMHR2 (HGNC:465): (anti-Mullerian hormone receptor type 2) This gene encodes the receptor for the anti-Mullerian hormone (AMH) which, in addition to testosterone, results in male sex differentiation. AMH and testosterone are produced in the testes by different cells and have different effects. Testosterone promotes the development of male genitalia while the binding of AMH to the encoded receptor prevents the development of the mullerian ducts into uterus and Fallopian tubes. Mutations in this gene are associated with persistent Mullerian duct syndrome type II. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Sep 2009]

AMHR2 Gene-Disease associations (from GenCC):

• persistent Mullerian duct syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0739 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020547.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMHR2	NM_020547.3	MANE Select	c.853-588C>T		intron	N/A	NP_065434.1	Q16671-1
	AMHR2	NM_001164690.2		c.853-588C>T		intron	N/A	NP_001158162.1	Q16671-2
	AMHR2	NM_001164691.2		c.853-588C>T		intron	N/A	NP_001158163.1	Q16671-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMHR2	ENST00000257863.9	TSL:1 MANE Select	c.853-588C>T		intron	N/A	ENSP00000257863.3	Q16671-1
	AMHR2	ENST00000379791.7	TSL:1	c.853-588C>T		intron	N/A	ENSP00000369117.3	Q16671-3
	AMHR2	ENST00000550311.5	TSL:1	c.853-588C>T		intron	N/A	ENSP00000446661.1	Q16671-2

Frequencies

GnomAD3 genomes AF: 0.0464 AC: 7062 AN: 152180 Hom.: 214 Cov.: 32

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0378

Gnomad ASJ AF: 0.0476

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.0395

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0756

Gnomad OTH AF: 0.0454

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0464 AC: 7061 AN: 152298 Hom.: 214 Cov.: 32 AF XY: 0.0438 AC XY: 3260 AN XY: 74466

African (AFR) AF: 0.0131 AC: 546 AN: 41564

American (AMR) AF: 0.0377 AC: 577 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0476 AC: 165 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.0180 AC: 87 AN: 4826

European-Finnish (FIN) AF: 0.0395 AC: 419 AN: 10614

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0756 AC: 5141 AN: 68012

Other (OTH) AF: 0.0449 AC: 95 AN: 2116

Alfa AF: 0.0462 Hom.: 114

Bravo AF: 0.0446

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.8
DANN	Benign	0.74
PhyloP100		0.0090
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs11170553; hg19: chr12-53822092;