chr3-180948769-A-C

Variant names:

• chr3-180948769-A-C
• rs3026195
• NM_005087.4:c.468A>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_005087.4(FXR1):​c.468A>C​(p.Ala156Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,432,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. A156A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FXR1 NM_005087.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132
• Publications: 0 publications found

Genes affected

FXR1 (HGNC:4023): (FMR1 autosomal homolog 1) The protein encoded by this gene is an RNA binding protein that interacts with the functionally-similar proteins FMR1 and FXR2. These proteins shuttle between the nucleus and cytoplasm and associate with polyribosomes, predominantly with the 60S ribosomal subunit. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

FXR1 Gene-Disease associations (from GenCC):

• congenital myopathy

  Inheritance: AR Classification: STRONG Submitted by: G2P
• myopathy, congenital, with respiratory insufficiency and bone fractures

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• myopathy, congenital proximal, with minicore lesions

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=-0.132 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005087.4. 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
	FXR1	NM_005087.4	MANE Select	c.468A>C	p.Ala156Ala	synonymous	Exon 6 of 17	NP_005078.2	P51114-1
	FXR1	NM_001441509.1		c.468A>C	p.Ala156Ala	synonymous	Exon 6 of 17	NP_001428438.1
	FXR1	NM_001441510.1		c.468A>C	p.Ala156Ala	synonymous	Exon 6 of 16	NP_001428439.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXR1	ENST00000357559.9	TSL:1 MANE Select	c.468A>C	p.Ala156Ala	synonymous	Exon 6 of 17	ENSP00000350170.3	P51114-1
	FXR1	ENST00000445140.6	TSL:1	c.468A>C	p.Ala156Ala	synonymous	Exon 6 of 16	ENSP00000388828.2	P51114-2
	FXR1	ENST00000963215.1		c.468A>C	p.Ala156Ala	synonymous	Exon 6 of 17	ENSP00000633274.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1432348 Hom.: 0 Cov.: 26 AF XY: 0.00000140 AC XY: 1 AN XY: 714342

African (AFR) AF: 0.00 AC: 0 AN: 32906

American (AMR) AF: 0.00 AC: 0 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25952

East Asian (EAS) AF: 0.00 AC: 0 AN: 39462

South Asian (SAS) AF: 0.00 AC: 0 AN: 85670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00000184 AC: 2 AN: 1085182

Other (OTH) AF: 0.00 AC: 0 AN: 59396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	3.9
DANN	Benign	0.69
PhyloP100		-0.13

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: rs3026195; hg19: chr3-180666557;