Genetic Variant FAM20A:p.Leu13Leu (chr17-68600628-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_017565.4(FAM20A):c.39G>A(p.Leu13Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0398 in 1,560,538 control chromosomes in the GnomAD database, including 2,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 189 hom., cov: 32)

Exomes 𝑓: 0.040 ( 1998 hom. )

Consequence

FAM20A
NM_017565.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.76

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 17-68600628-C-T is Benign according to our data. Variant chr17-68600628-C-T is described in ClinVar as Benign. ClinVar VariationId is 260832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.76 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM20A	NM_017565.4 link	c.39G>A	p.Leu13Leu	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.39G>A	p.Leu13Leu	synonymous_variant	Exon 1 of 11	1	NM_017565.4	ENSP00000468308.1		Q96MK3

Frequencies

GnomAD3 genomes

AF:

0.0402

AC:

6117

AN:

152126

Hom.:

188

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0447

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0218

Gnomad ASJ

AF:

0.0259

Gnomad EAS

AF:

0.112

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.0394

Gnomad MID

AF:

0.0350

Gnomad NFE

AF:

0.0294

Gnomad OTH

AF:

0.0353

GnomAD2 exomes

AF:

0.0525

AC:

8449

AN:

161032

AF XY:

0.0586

show subpopulations

Gnomad AFR exome

AF:

0.0430

Gnomad AMR exome

AF:

0.0122

Gnomad ASJ exome

AF:

0.0222

Gnomad EAS exome

AF:

0.116

Gnomad FIN exome

AF:

0.0348

Gnomad NFE exome

AF:

0.0300

Gnomad OTH exome

AF:

0.0383

GnomAD4 exome

AF:

0.0398

AC:

56044

AN:

1408296

Hom.:

1998

Cov.:

AF XY:

0.0426

AC XY:

29695

AN XY:

696574

show subpopulations

African (AFR)

AF:

0.0443

AC:

1446

AN:

32652

American (AMR)

AF:

0.0140

AC:

528

AN:

37674

Ashkenazi Jewish (ASJ)

AF:

0.0235

AC:

593

AN:

25272

East Asian (EAS)

AF:

0.144

AC:

5420

AN:

37742

South Asian (SAS)

AF:

0.144

AC:

11633

AN:

80652

European-Finnish (FIN)

AF:

0.0315

AC:

1290

AN:

40912

Middle Eastern (MID)

AF:

0.0425

AC:

182

AN:

4278

European-Non Finnish (NFE)

AF:

0.0298

AC:

32496

AN:

1090482

Other (OTH)

AF:

0.0419

AC:

2456

AN:

58632

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

3335

6670

10004

13339

16674

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1392

2784

4176

5568

6960

<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:

0.0402

AC:

6122

AN:

152242

Hom.:

189

Cov.:

AF XY:

0.0432

AC XY:

3213

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0447

AC:

1857

AN:

41572

American (AMR)

AF:

0.0219

AC:

335

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0259

AC:

AN:

3472

East Asian (EAS)

AF:

0.112

AC:

573

AN:

5126

South Asian (SAS)

AF:

0.156

AC:

751

AN:

4828

European-Finnish (FIN)

AF:

0.0394

AC:

418

AN:

10614

Middle Eastern (MID)

AF:

0.0377

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0294

AC:

1998

AN:

68002

Other (OTH)

AF:

0.0373

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

288

575

863

1150

1438

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<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:

0.0308

Hom.:

Bravo

AF:

0.0372

Asia WGS

AF:

0.119

AC:

412

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 11, 2018

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

-0.53

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

1.8

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