rs1557178460

Variant names:

• chrX-147930216-G-A
• NM_002024.6:c.602G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-147930216-G-A
• chrX-147930216-G-C

Variant summary

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

The NM_002024.6(FMR1):​c.602G>A​(p.Arg201Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000923 in 1,083,475 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: FMR1 NM_002024.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.82

Genes affected

FMR1 (HGNC:3775): (fragile X messenger ribonucleoprotein 1) The protein encoded by this gene binds RNA and is associated with polysomes. The encoded protein may be involved in mRNA trafficking from the nucleus to the cytoplasm. A trinucleotide repeat (CGG) in the 5' UTR is normally found at 6-53 copies, but an expansion to 55-230 repeats is the cause of fragile X syndrome. Expansion of the trinucleotide repeat may also cause one form of premature ovarian failure (POF1). Multiple alternatively spliced transcript variants that encode different protein isoforms and which are located in different cellular locations have been described for this gene. [provided by RefSeq, May 2010]

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 rank	MANE	Protein	UniProt
FMR1	NM_002024.6	c.602G>A	p.Arg201Lys	missense_variant	Exon 7 of 17	ENST00000370475.9	NP_002015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMR1	ENST00000370475.9	c.602G>A	p.Arg201Lys	missense_variant	Exon 7 of 17	1	NM_002024.6	ENSP00000359506.5

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.23e-7 AC: 1 AN: 1083475 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 349519

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: 0.00000121

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T;.;.;.;.;T;T;.;D;T;T;.
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;.;D;D;D;D;D
M_CAP	Pathogenic	0.50	D
MetaRNN	Uncertain	0.61	D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	1.9	.;L;L;L;.;.;.;.;L;.;.;L
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-2.3	.;N;N;.;N;.;N;N;N;.;.;N
REVEL	Benign	0.20
Sift	Benign	0.12	.;T;T;.;T;.;T;T;T;.;.;T
Sift4G	Benign	0.14	T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.98, 0.97, 0.26	.;.;.;D;.;D;D;D;B;.;.;.
Vest4		0.49
MutPred		0.47		Gain of ubiquitination at R201 (P = 0.0094);Gain of ubiquitination at R201 (P = 0.0094);Gain of ubiquitination at R201 (P = 0.0094);Gain of ubiquitination at R201 (P = 0.0094);Gain of ubiquitination at R201 (P = 0.0094);Gain of ubiquitination at R201 (P = 0.0094);Gain of ubiquitination at R201 (P = 0.0094);Gain of ubiquitination at R201 (P = 0.0094);Gain of ubiquitination at R201 (P = 0.0094);Gain of ubiquitination at R201 (P = 0.0094);.;Gain of ubiquitination at R201 (P = 0.0094);
MVP		0.63
MPC		1.1
ClinPred		0.95	D
GERP RS		5.1
Varity_R		0.85
gMVP		0.78

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-147011735;