rs149670651

Variant names:

• chrX-136207901-C-G
• NM_001159702.3:c.441C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-136207901-C-G
• chrX-136207901-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001159699.2(FHL1):​c.489C>G​(p.Asp163Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,172 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: FHL1 NM_001159699.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.351

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20464066).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHL1	NM_001159702.3	c.441C>G	p.Asp147Glu	missense_variant	Exon 5 of 8	ENST00000394155.8	NP_001153174.1
FHL1	NM_001159699.2	c.489C>G	p.Asp163Glu	missense_variant	Exon 4 of 6	ENST00000370683.6	NP_001153171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FHL1	ENST00000394155.8	c.441C>G	p.Asp147Glu	missense_variant	Exon 5 of 8	5	NM_001159702.3	ENSP00000377710.2
FHL1	ENST00000370683.6	c.489C>G	p.Asp163Glu	missense_variant	Exon 4 of 6	1	NM_001159699.2	ENSP00000359717.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098172 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363528

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: 0.0000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.22	.;T;.;T;.;T;T;T;.;T;.;T;.;.;T;.;T;.;.;T;T;.
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.80	.;T;.;T;T;T;T;T;.;.;.;T;.;T;T;T;.;T;T;T;T;.
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.17	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	0.41	N;N;N;.;N;.;.;.;N;.;N;.;N;N;.;.;N;.;.;.;.;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.47	.;N;N;.;.;N;N;.;.;N;N;N;N;N;N;.;N;N;N;N;N;.
REVEL	Benign	0.24
Sift	Benign	0.44	.;T;T;.;.;T;T;.;.;T;T;T;T;T;T;.;T;T;T;T;T;.
Sift4G	Benign	1.0	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.040, 0.0	.;B;.;.;.;.;.;.;.;.;.;.;.;.;.;.;B;.;.;B;.;.
Vest4		0.28
MutPred		0.28		Gain of methylation at K144 (P = 0.0828);Gain of methylation at K144 (P = 0.0828);Gain of methylation at K144 (P = 0.0828);Gain of methylation at K144 (P = 0.0828);Gain of methylation at K144 (P = 0.0828);Gain of methylation at K144 (P = 0.0828);Gain of methylation at K144 (P = 0.0828);Gain of methylation at K144 (P = 0.0828);Gain of methylation at K144 (P = 0.0828);Gain of methylation at K144 (P = 0.0828);Gain of methylation at K144 (P = 0.0828);Gain of methylation at K144 (P = 0.0828);Gain of methylation at K144 (P = 0.0828);Gain of methylation at K144 (P = 0.0828);Gain of methylation at K144 (P = 0.0828);Gain of methylation at K144 (P = 0.0828);Gain of methylation at K144 (P = 0.0828);.;.;.;Gain of methylation at K144 (P = 0.0828);Gain of methylation at K144 (P = 0.0828);
MVP		0.82
MPC		0.46
ClinPred		0.33	T
GERP RS		4.8
Varity_R		0.19

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-135290060;