rs35489610

Variant names:

• chrX-136151292-T-TA
• rs35489610
• NM_001159702.3:c.-101+3665dupA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001159702.3(FHL1):​c.-101+3665dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.69 (19068 hom., 23694 hem., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: FHL1 NM_001159702.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183
• Publications: 1 publications found

Genes affected

FHL1 (HGNC:3702): (four and a half LIM domains 1) This gene encodes a member of the four-and-a-half-LIM-only protein family. Family members contain two highly conserved, tandemly arranged, zinc finger domains with four highly conserved cysteines binding a zinc atom in each zinc finger. Expression of these family members occurs in a cell- and tissue-specific mode and these proteins are involved in many cellular processes. Mutations in this gene have been found in patients with Emery-Dreifuss muscular dystrophy. Multiple alternately spliced transcript variants which encode different protein isoforms have been described.[provided by RefSeq, Nov 2009]

FHL1 Gene-Disease associations (from GenCC):

• X-linked myopathy with postural muscle atrophy

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• myopathy, reducing body, X-linked, early-onset, severe

  Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• reducing body myopathy

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• X-linked Emery-Dreifuss muscular dystrophy

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• X-linked scapuloperoneal muscular dystrophy

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159702.3. 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
	FHL1	NM_001159702.3	MANE Plus Clinical	c.-101+3665dupA		intron	N/A	NP_001153174.1	Q13642-2
	FHL1	NM_001369326.1		c.-101+3415dupA		intron	N/A	NP_001356255.1	Q13642-2
	FHL1	NM_001369327.2		c.-101+3147dupA		intron	N/A	NP_001356256.1	Q13642-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHL1	ENST00000394155.8	TSL:5 MANE Plus Clinical	c.-101+3664_-101+3665insA		intron	N/A	ENSP00000377710.2	Q13642-2
	FHL1	ENST00000651089.1		c.-243+3414_-243+3415insA		intron	N/A	ENSP00000498684.1	Q13642-2
	FHL1	ENST00000629039.2	TSL:2	c.-101+4280_-101+4281insA		intron	N/A	ENSP00000486439.1	Q13642-1

Frequencies

GnomAD3 genomes AF: 0.690 AC: 77306 AN: 111974 Hom.: 19066 Cov.: 0

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.641

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.651

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.690 AC: 77338 AN: 112029 Hom.: 19068 Cov.: 0 AF XY: 0.692 AC XY: 23694 AN XY: 34221

African (AFR) AF: 0.521 AC: 16080 AN: 30891

American (AMR) AF: 0.676 AC: 7182 AN: 10627

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 1803 AN: 2652

East Asian (EAS) AF: 0.616 AC: 2175 AN: 3530

South Asian (SAS) AF: 0.667 AC: 1801 AN: 2701

European-Finnish (FIN) AF: 0.823 AC: 4963 AN: 6032

Middle Eastern (MID) AF: 0.620 AC: 134 AN: 216

European-Non Finnish (NFE) AF: 0.784 AC: 41707 AN: 53172

Other (OTH) AF: 0.651 AC: 996 AN: 1529

Alfa AF: 0.744 Hom.: 6123

Bravo AF: 0.673

Asia WGS AF: 0.619 AC: 1562 AN: 2522

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs35489610;

hg19: chrX-135233451;