chrX-136147571-C-A

Variant names:

• chrX-136147571-C-A
• rs777858178
• NM_001159702.3:c.-158C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001159702.3(FHL1):​c.-158C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000093 (0 hom., 0 hem., cov: 20)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: FHL1 NM_001159702.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233
• Publications: 0 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), G2P, Orphanet
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

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.-158C>A		5_prime_UTR	Exon 1 of 8	NP_001153174.1	Q13642-2
	FHL1	NM_001449.5		c.-158C>A		5_prime_UTR	Exon 1 of 7	NP_001440.2
	FHL1	NM_001159703.2		c.-158C>A		5_prime_UTR	Exon 1 of 6	NP_001153175.1	Q13642-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHL1	ENST00000394155.8	TSL:5 MANE Plus Clinical	c.-158C>A		5_prime_UTR	Exon 1 of 8	ENSP00000377710.2	Q13642-2
	FHL1	ENST00000651929.2		c.-158C>A		5_prime_UTR	Exon 1 of 7	ENSP00000499016.1	Q13642-1
	FHL1	ENST00000652457.1		c.-158C>A		5_prime_UTR	Exon 1 of 8	ENSP00000498503.1	A0A494C0D6

Frequencies

GnomAD3 genomes AF: 0.00000926 AC: 1 AN: 108014 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000194

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1623 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 689

African (AFR) AF: 0.00 AC: 0 AN: 17

American (AMR) AF: 0.00 AC: 0 AN: 5

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7

East Asian (EAS) AF: 0.00 AC: 0 AN: 37

South Asian (SAS) AF: 0.00 AC: 0 AN: 635

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 871

Other (OTH) AF: 0.00 AC: 0 AN: 36

GnomAD4 genome AF: 0.00000926 AC: 1 AN: 108014 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 31186

African (AFR) AF: 0.00 AC: 0 AN: 29902

American (AMR) AF: 0.00 AC: 0 AN: 10451

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2603

East Asian (EAS) AF: 0.00 AC: 0 AN: 3340

South Asian (SAS) AF: 0.00 AC: 0 AN: 2542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5303

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 227

European-Non Finnish (NFE) AF: 0.0000194 AC: 1 AN: 51551

Other (OTH) AF: 0.00 AC: 0 AN: 1450

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Benign	0.90
PhyloP100		-0.23
PromoterAI		0.14	Neutral

Splicing

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

Other links and lift over

dbSNP: rs777858178; hg19: chrX-135229730;