rs986099

Variant names:

• chr17-68600322-C-A
• rs986099
• NM_017565.4:c.345G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-68600322-C-A
• chr17-68600322-C-G
• chr17-68600322-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6 BP7

The NM_017565.4(FAM20A):​c.345G>T​(p.Ser115Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000626 in 1,438,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S115S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: FAM20A NM_017565.4 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.149
• Publications: 5 publications found

Genes affected

FAM20A (HGNC:23015): (FAM20A golgi associated secretory pathway pseudokinase) This locus encodes a protein that is likely secreted and may function in hematopoiesis. A mutation at this locus has been associated with amelogenesis imperfecta and gingival hyperplasia syndrome. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Aug 2011]

LINC01482 (HGNC:51128): (long intergenic non-protein coding RNA 1482)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 17-68600322-C-A is Benign according to our data. Variant chr17-68600322-C-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 2980264.
• BP7: Synonymous conserved (PhyloP=0.149 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017565.4. 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
	FAM20A	NM_017565.4	MANE Select	c.345G>T	p.Ser115Ser	synonymous	Exon 1 of 11	NP_060035.2	Q96MK3
	FAM20A	NM_001243746.2		c.-296G>T		5_prime_UTR	Exon 1 of 12	NP_001230675.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM20A	ENST00000592554.2	TSL:1 MANE Select	c.345G>T	p.Ser115Ser	synonymous	Exon 1 of 11	ENSP00000468308.1	Q96MK3
	FAM20A	ENST00000882126.1		c.345G>T	p.Ser115Ser	synonymous	Exon 1 of 12	ENSP00000552185.1
	FAM20A	ENST00000882123.1		c.345G>T	p.Ser115Ser	synonymous	Exon 1 of 10	ENSP00000552182.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000149 AC: 3 AN: 201240 AF XY: 0.0000273

Gnomad AFR exome AF: 0.0000911

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000234

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000626 AC: 9 AN: 1438010 Hom.: 0 Cov.: 33 AF XY: 0.00000701 AC XY: 5 AN XY: 713212

African (AFR) AF: 0.0000304 AC: 1 AN: 32878

American (AMR) AF: 0.00 AC: 0 AN: 41834

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25622

East Asian (EAS) AF: 0.00 AC: 0 AN: 38170

South Asian (SAS) AF: 0.00 AC: 0 AN: 82546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00000727 AC: 8 AN: 1100812

Other (OTH) AF: 0.00 AC: 0 AN: 59472

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000177 Hom.: 623

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	-	Amelogenesis imperfecta type 1G (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	14
DANN	Benign	0.92
PhyloP100		0.15

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: rs986099; hg19: chr17-66596463;