12-53423957-G-C

Position:

• chr12-53423957-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020547.3(AMHR2):​c.23G>C​(p.Trp8Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AMHR2 NM_020547.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.18

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMHR2	NM_020547.3	c.23G>C	p.Trp8Ser	missense_variant	1/11	ENST00000257863.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMHR2	ENST00000257863.9	c.23G>C	p.Trp8Ser	missense_variant	1/11	1	NM_020547.3	P1
AMHR2	ENST00000379791.7	c.23G>C	p.Trp8Ser	missense_variant	1/9	1
AMHR2	ENST00000550311.5	c.23G>C	p.Trp8Ser	missense_variant	1/11	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2023

The c.23G>C (p.W8S) alteration is located in exon 1 (coding exon 1) of the AMHR2 gene. This alteration results from a G to C substitution at nucleotide position 23, causing the tryptophan (W) at amino acid position 8 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T;.;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.69	D;D;D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Benign	0.81	L;L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Pathogenic	0.72
Sift	Benign	0.030	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.96	D;.;.
Vest4		0.61
MutPred		0.69		Gain of catalytic residue at S4 (P = 2e-04);Gain of catalytic residue at S4 (P = 2e-04);Gain of catalytic residue at S4 (P = 2e-04);
MVP		0.98
MPC		0.33
ClinPred		0.91	D
GERP RS		4.9
Varity_R		0.34
gMVP		0.64

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: chr12-53817741;