rs530034797

Variant names:

• chrX-67545233-C-A
• NM_000044.6:c.87C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-67545233-C-A
• chrX-67545233-C-G
• chrX-67545233-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_000044.6(AR):​c.87C>A​(p.Ser29Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S29S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 21)
• Consequence: AR NM_000044.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860

Genes affected

AR (HGNC:644): (androgen receptor) The androgen receptor gene is more than 90 kb long and codes for a protein that has 3 major functional domains: the N-terminal domain, DNA-binding domain, and androgen-binding domain. The protein functions as a steroid-hormone activated transcription factor. Upon binding the hormone ligand, the receptor dissociates from accessory proteins, translocates into the nucleus, dimerizes, and then stimulates transcription of androgen responsive genes. This gene contains 2 polymorphic trinucleotide repeat segments that encode polyglutamine and polyglycine tracts in the N-terminal transactivation domain of its protein. Expansion of the polyglutamine tract from the normal 9-34 repeats to the pathogenic 38-62 repeats causes spinal bulbar muscular atrophy (SBMA, also known as Kennedy's disease). Mutations in this gene are also associated with complete androgen insensitivity (CAIS). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.812

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AR	NM_000044.6	c.87C>A	p.Ser29Arg	missense_variant	Exon 1 of 8	ENST00000374690.9	NP_000035.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AR	ENST00000374690.9	c.87C>A	p.Ser29Arg	missense_variant	Exon 1 of 8	1	NM_000044.6	ENSP00000363822.3

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	.;.;.;T;.
FATHMM_MKL	Benign	0.51	D
LIST_S2	Uncertain	0.95	D;D;D;D;D
M_CAP	Pathogenic	0.49	D
MetaRNN	Pathogenic	0.81	D;D;D;D;D
MetaSVM	Uncertain	0.52	D
MutationAssessor	Benign	1.8	.;L;L;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.8	N;N;N;.;.
REVEL	Pathogenic	0.73
Sift	Uncertain	0.0010	D;D;D;.;.
Sift4G	Uncertain	0.010	D;D;D;T;T
Vest4		0.69
MutPred		0.76		Gain of MoRF binding (P = 0.0249);Gain of MoRF binding (P = 0.0249);Gain of MoRF binding (P = 0.0249);Gain of MoRF binding (P = 0.0249);Gain of MoRF binding (P = 0.0249);
MVP		0.95
MPC		1.0
ClinPred		0.95	D
GERP RS		0.64
Varity_R		0.80
gMVP		0.89

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: chrX-66765075;