15-99105549-AG-TA

Variant names:

• chr15-99105549-AG-TA
• NM_145728.3:c.350_351delAGinsTA
• SYNM p.Gln117Leu

Variant summary

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

The NM_145728.3(SYNM):​c.350_351delAGinsTA​(p.Gln117Leu) variant causes a missense change involving the alteration of a non-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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q117H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYNM NM_145728.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.511
• Publications: 0 publications found

Genes affected

SYNM (HGNC:24466): (synemin) The protein encoded by this gene is an intermediate filament (IF) family member. IF proteins are cytoskeletal proteins that confer resistance to mechanical stress and are encoded by a dispersed multigene family. This protein has been found to form a linkage between desmin, which is a subunit of the IF network, and the extracellular matrix, and provides an important structural support in muscle. Two alternatively spliced variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

SYNM-AS1 (HGNC:55421): (SYNM antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145728.3. 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
	SYNM	NM_145728.3	MANE Select	c.350_351delAGinsTA	p.Gln117Leu	missense	N/A	NP_663780.2	O15061-1
	SYNM	NM_015286.6		c.350_351delAGinsTA	p.Gln117Leu	missense	N/A	NP_056101.5
	SYNM-AS1	NR_187219.1		n.190+138_190+139delCTinsTA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNM	ENST00000336292.11	TSL:1 MANE Select	c.350_351delAGinsTA	p.Gln117Leu	missense	N/A	ENSP00000336775.7	O15061-1
	SYNM	ENST00000594047.2	TSL:1	c.350_351delAGinsTA	p.Gln117Leu	missense	N/A	ENSP00000472953.1	O15061-2
	SYNM	ENST00000328642.11	TSL:1	c.350_351delAGinsTA	p.Gln117Leu	missense	N/A	ENSP00000330469.8	O15061-3

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		0.51

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: chr15-99645755;