6-96610584-GGT-AGC

Variant names:

• chr6-96610584-GGT-AGC
• NM_001322466.2:c.517_519delGGTinsAGC
• FHL5 p.Gly173Ser

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001322466.2(FHL5):​c.517_519delGGTinsAGC​(p.Gly173Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FHL5 NM_001322466.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.56
• Publications: 0 publications found

Genes affected

FHL5 (HGNC:17371): (four and a half LIM domains 5) The protein encoded by this gene is coordinately expressed with activator of cAMP-responsive element modulator (CREM). It is associated with CREM and confers a powerful transcriptional activation function. CREM acts as a transcription factor essential for the differentiation of spermatids into mature spermatozoa. There are multiple polyadenylation sites found in this gene. Polymorphisms in this gene may be associated with susceptibility for migraine headaches. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Apr 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001322466.2. 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
	FHL5	NM_001322466.2	MANE Select	c.517_519delGGTinsAGC	p.Gly173Ser	missense	N/A	NP_001309395.1	Q5TD97
	FHL5	NM_001170807.3		c.517_519delGGTinsAGC	p.Gly173Ser	missense	N/A	NP_001164278.1	Q5TD97
	FHL5	NM_001322467.1		c.517_519delGGTinsAGC	p.Gly173Ser	missense	N/A	NP_001309396.1	Q5TD97

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHL5	ENST00000450218.6	TSL:5 MANE Select	c.517_519delGGTinsAGC	p.Gly173Ser	missense	N/A	ENSP00000396390.2	Q5TD97
	FHL5	ENST00000326771.2	TSL:1	c.517_519delGGTinsAGC	p.Gly173Ser	missense	N/A	ENSP00000326022.2	Q5TD97
	FHL5	ENST00000541107.5	TSL:1	c.517_519delGGTinsAGC	p.Gly173Ser	missense	N/A	ENSP00000442357.1	Q5TD97

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.6

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

hg19: chr6-97058460;