Genetic Variant FAM20A:p.Ser115Ser (chr17-68600322-C-T) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.149

Publications

5 publications found

Variant links:

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]

FAM20A links:

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

LINC01482 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM20A	NM_017565.4 link	c.345G>A	p.Ser115Ser	synonymous_variant	Exon 1 of 11	ENST00000592554.2	NP_060035.2	Q96MK3L8B8N7Q8IYA5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM20A	ENST00000592554.2 link	c.345G>A	p.Ser115Ser	synonymous_variant	Exon 1 of 11	1	NM_017565.4	ENSP00000468308.1		Q96MK3

Frequencies

GnomAD3 genomes

AF:

0.149

AC:

22582

AN:

152038

Hom.:

1881

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.160

AC XY:

114188

AN XY:

713110

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

11615

23230

34844

46459

58074

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6352

12704

19056

25408

31760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.148

AC:

22588

AN:

152156

Hom.:

1882

Cov.:

AF XY:

0.149

AC XY:

11118

AN XY:

74384

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.161

AC:

10934

AN:

67966

Other (OTH)

AF:

0.156

AC:

330

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1006

2012

3018

4024

5030

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

256

512

768

1024

1280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.128

Hom.:

623

Bravo

AF:

0.151

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 18, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over