rs2076705

Positions:

• chrX-136209863-C-A
• chrX-136209863-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001159702.3(FHL1):​c.889-8C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 20)
• Consequence: FHL1 NM_001159702.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00009213
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.111

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant X-136209863-C-A is Benign according to our data. Variant chrX-136209863-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1533726.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FHL1	NM_001159699.2	c.737-8C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000370683.6
FHL1	NM_001159702.3	c.889-8C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000394155.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FHL1	ENST00000370683.6	c.737-8C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001159699.2	P1
FHL1	ENST00000394155.8	c.889-8C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_001159702.3

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 20

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

X-linked myopathy with postural muscle atrophy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

May 12, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.047
DANN	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000092
dbscSNV1_RF	Benign	0.032
SpliceAI score (max)		0.010		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-135292022;