15-99105481-G-A

Variant names:

• chr15-99105481-G-A
• rs1217253530
• NM_145728.3:c.282G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_145728.3(SYNM):​c.282G>A​(p.Glu94Glu) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SYNM NM_145728.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14
• Publications: 2 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=2.14 with no splicing effect.

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.282G>A	p.Glu94Glu	synonymous	Exon 1 of 4	NP_663780.2	O15061-1
	SYNM	NM_015286.6		c.282G>A	p.Glu94Glu	synonymous	Exon 1 of 5	NP_056101.5
	SYNM-AS1	NR_187219.1		n.190+207C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNM	ENST00000336292.11	TSL:1 MANE Select	c.282G>A	p.Glu94Glu	synonymous	Exon 1 of 4	ENSP00000336775.7	O15061-1
	SYNM	ENST00000594047.2	TSL:1	c.282G>A	p.Glu94Glu	synonymous	Exon 1 of 5	ENSP00000472953.1	O15061-2
	SYNM	ENST00000328642.11	TSL:1	c.282G>A	p.Glu94Glu	synonymous	Exon 1 of 4	ENSP00000330469.8	O15061-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1217232 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 595508

African (AFR) AF: 0.00 AC: 0 AN: 24362

American (AMR) AF: 0.00 AC: 0 AN: 15858

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18710

East Asian (EAS) AF: 0.00 AC: 0 AN: 26488

South Asian (SAS) AF: 0.00 AC: 0 AN: 53478

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28754

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3476

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 996646

Other (OTH) AF: 0.00 AC: 0 AN: 49460

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.5
DANN	Benign	0.97
PhyloP100		2.1
PromoterAI		-0.029	Neutral

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

Other links and lift over

dbSNP: rs1217253530; hg19: chr15-99645687;