NM_017565.4:c.345G>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS1

The NM_017565.4(FAM20A):​c.345G>C​(p.Ser115Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000339 in 1,590,192 control chromosomes in the GnomAD database, including 2 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 0.0019 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: FAM20A NM_017565.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 17-68600322-C-G is Benign according to our data. Variant chr17-68600322-C-G is described in ClinVar as Benign. ClinVar VariationId is 734418.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.149 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00191 (291/152184) while in subpopulation AFR AF = 0.00674 (280/41538). AF 95% confidence interval is 0.00609. There are 1 homozygotes in GnomAd4. There are 158 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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

Frequencies

GnomAD3 genomes AF: 0.00191 AC: 290 AN: 152066 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00674

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000398 AC: 80 AN: 201240 AF XY: 0.000336

Gnomad AFR exome AF: 0.00656

Gnomad AMR exome AF: 0.000226

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000117

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000172 AC: 248 AN: 1438008 Hom.: 1 Cov.: 33 AF XY: 0.000140 AC XY: 100 AN XY: 713210

African (AFR) AF: 0.00645 AC: 212 AN: 32876

American (AMR) AF: 0.000191 AC: 8 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: 0.0000121 AC: 1 AN: 82546

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

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5730

European-Non Finnish (NFE) AF: 0.00000636 AC: 7 AN: 1100812

Other (OTH) AF: 0.000319 AC: 19 AN: 59472

GnomAD4 genome AF: 0.00191 AC: 291 AN: 152184 Hom.: 1 Cov.: 32 AF XY: 0.00212 AC XY: 158 AN XY: 74402

African (AFR) AF: 0.00674 AC: 280 AN: 41538

American (AMR) AF: 0.000523 AC: 8 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5122

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67984

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.0000177 Hom.: 623

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Benign	0.89
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism

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;