1-37998998-C-A

Variant names:

• chr1-37998998-C-A
• rs61732084
• NM_004468.5:c.307G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004468.5(FHL3):​c.307G>T​(p.Ala103Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A103T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FHL3 NM_004468.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.96
• Publications: 0 publications found

Genes affected

FHL3 (HGNC:3704): (four and a half LIM domains 3) The protein encoded by this gene is a member of a family of proteins containing a four-and-a-half LIM domain, which is a highly conserved double zinc finger motif. The encoded protein has been shown to interact with the cancer developmental regulators SMAD2, SMAD3, and SMAD4, the skeletal muscle myogenesis protein MyoD, and the high-affinity IgE beta chain regulator MZF-1. This protein may be involved in tumor suppression, repression of MyoD expression, and repression of IgE receptor expression. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004468.5. 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
	FHL3	NM_004468.5	MANE Select	c.307G>T	p.Ala103Ser	missense	Exon 3 of 6	NP_004459.2	Q13643
	FHL3	NM_001243878.2		c.-18G>T		5_prime_UTR	Exon 2 of 5	NP_001230807.1	Q96C98

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHL3	ENST00000373016.4	TSL:1 MANE Select	c.307G>T	p.Ala103Ser	missense	Exon 3 of 6	ENSP00000362107.3	Q13643
	FHL3	ENST00000485803.5	TSL:1	n.297G>T		non_coding_transcript_exon	Exon 2 of 5
	FHL3	ENST00000850578.1		c.307G>T	p.Ala103Ser	missense	Exon 3 of 6	ENSP00000520866.1	Q13643

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Benign	0.88	L
PhyloP100		5.0
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.52	N
REVEL	Uncertain	0.43
Sift	Benign	0.077	T
Sift4G	Benign	0.72	T
Polyphen		0.65	P
Vest4		0.41
MutPred		0.35		Gain of disorder (P = 0.0191)
MVP		0.69
MPC		0.62
ClinPred		0.65	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.050
gMVP		0.34
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs61732084; hg19: chr1-38464670;