Variant rs2302235 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017565.4(FAM20A):c.929-112C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,154,794 control chromosomes in the GnomAD database, including 11,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1396 hom., cov: 32)

Exomes 𝑓: 0.14 ( 10061 hom. )

Consequence

FAM20A
NM_017565.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.493

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:

PRKAR1A (HGNC:9388): (protein kinase cAMP-dependent type I regulatory subunit alpha) cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent protein kinase, which transduces the signal through phosphorylation of different target proteins. The inactive kinase holoenzyme is a tetramer composed of two regulatory and two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Four different regulatory subunits and three catalytic subunits have been identified in humans. This gene encodes one of the regulatory subunits. This protein was found to be a tissue-specific extinguisher that down-regulates the expression of seven liver genes in hepatoma x fibroblast hybrids. Mutations in this gene cause Carney complex (CNC). This gene can fuse to the RET protooncogene by gene rearrangement and form the thyroid tumor-specific chimeric oncogene known as PTC2. A nonconventional nuclear localization sequence (NLS) has been found for this protein which suggests a role in DNA replication via the protein serving as a nuclear transport protein for the second subunit of the Replication Factor C (RFC40). Several alternatively spliced transcript variants encoding two different isoforms have been observed. [provided by RefSeq, Jan 2013]

PRKAR1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 17-68542277-G-A is Benign according to our data. Variant chr17-68542277-G-A is described in ClinVar as [Benign]. Clinvar id is 1237093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM20A	NM_017565.4 linkuse as main transcript	c.929-112C>T		intron_variant		ENST00000592554.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM20A	ENST00000592554.2 linkuse as main transcript	c.929-112C>T		intron_variant		1	NM_017565.4	P1

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

20316

AN:

152022

Hom.:

1396

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.170

Gnomad SAS

AF:

0.199

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.132

GnomAD4 exome

AF:

0.138

AC:

138355

AN:

1002654

Hom.:

10061

AF XY:

0.140

AC XY:

71572

AN XY:

509906

show subpopulations

Gnomad4 AFR exome

AF:

0.123

Gnomad4 AMR exome

AF:

0.170

Gnomad4 ASJ exome

AF:

0.117

Gnomad4 EAS exome

AF:

0.166

Gnomad4 SAS exome

AF:

0.191

Gnomad4 FIN exome

AF:

0.107

Gnomad4 NFE exome

AF:

0.133

Gnomad4 OTH exome

AF:

0.137

GnomAD4 genome

AF:

0.134

AC:

20320

AN:

152140

Hom.:

1396

Cov.:

AF XY:

0.134

AC XY:

9950

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.123

Gnomad4 AMR

AF:

0.154

Gnomad4 ASJ

AF:

0.120

Gnomad4 EAS

AF:

0.170

Gnomad4 SAS

AF:

0.198

Gnomad4 FIN

AF:

0.105

Gnomad4 NFE

AF:

0.133

Gnomad4 OTH

AF:

0.130

Alfa

AF:

0.137

Hom.:

304

Bravo

AF:

0.139

Asia WGS

AF:

0.187

AC:

649

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.4

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over