17-68600322-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_017565.4(FAM20A):​c.345G>A​(p.Ser115Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,589,980 control chromosomes in the GnomAD database, including 21,491 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S115S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.15 (1882 hom., cov: 32)
  • Exomes 𝑓: 0.16 (19609 hom.)
• Consequence: FAM20A NM_017565.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• 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: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 17-68600322-C-T is Benign according to our data. Variant chr17-68600322-C-T is described in ClinVar as Benign. ClinVar VariationId is 260831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

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>A	p.Ser115Ser	synonymous	Exon 1 of 11	NP_060035.2	Q96MK3
	FAM20A	NM_001243746.2		c.-296G>A		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>A	p.Ser115Ser	synonymous	Exon 1 of 11	ENSP00000468308.1	Q96MK3
	FAM20A	ENST00000882126.1		c.345G>A	p.Ser115Ser	synonymous	Exon 1 of 12	ENSP00000552185.1
	FAM20A	ENST00000882123.1		c.345G>A	p.Ser115Ser	synonymous	Exon 1 of 10	ENSP00000552182.1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22582 AN: 152038 Hom.: 1881 Cov.: 32

Gnomad AFR AF: 0.0977

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.159

GnomAD2 exomes AF: 0.177 AC: 35554 AN: 201240 AF XY: 0.170

Gnomad AFR exome AF: 0.0930

Gnomad AMR exome AF: 0.293

Gnomad ASJ exome AF: 0.140

Gnomad EAS exome AF: 0.275

Gnomad FIN exome AF: 0.132

Gnomad NFE exome AF: 0.158

Gnomad OTH exome AF: 0.178

GnomAD4 exome AF: 0.162 AC: 232391 AN: 1437824 Hom.: 19609 Cov.: 33 AF XY: 0.160 AC XY: 114188 AN XY: 713110

African (AFR) AF: 0.0940 AC: 3091 AN: 32870

American (AMR) AF: 0.283 AC: 11807 AN: 41786

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 3676 AN: 25620

East Asian (EAS) AF: 0.290 AC: 11057 AN: 38158

South Asian (SAS) AF: 0.120 AC: 9885 AN: 82532

European-Finnish (FIN) AF: 0.133 AC: 6754 AN: 50944

Middle Eastern (MID) AF: 0.141 AC: 807 AN: 5730

European-Non Finnish (NFE) AF: 0.160 AC: 175612 AN: 1100720

Other (OTH) AF: 0.163 AC: 9702 AN: 59464

GnomAD4 genome AF: 0.148 AC: 22588 AN: 152156 Hom.: 1882 Cov.: 32 AF XY: 0.149 AC XY: 11118 AN XY: 74384

African (AFR) AF: 0.0976 AC: 4054 AN: 41534

American (AMR) AF: 0.214 AC: 3270 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 491 AN: 3472

East Asian (EAS) AF: 0.278 AC: 1425 AN: 5118

South Asian (SAS) AF: 0.121 AC: 583 AN: 4830

European-Finnish (FIN) AF: 0.131 AC: 1393 AN: 10610

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10934 AN: 67966

Other (OTH) AF: 0.156 AC: 330 AN: 2116

Alfa AF: 0.128 Hom.: 623

Bravo AF: 0.151

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	14
DANN	Benign	0.94
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV73980328;