17-68537722-A-G
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1
The NM_017565.4(FAM20A):āc.1381T>Cā(p.Leu461=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,612,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ).
Frequency
Genomes: š 0.00059 ( 0 hom., cov: 32)
Exomes š: 0.000067 ( 0 hom. )
Consequence
FAM20A
NM_017565.4 synonymous
NM_017565.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.12
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]
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 17-68537722-A-G is Benign according to our data. Variant chr17-68537722-A-G is described in ClinVar as [Benign]. Clinvar id is 2085866.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.12 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000591 (90/152288) while in subpopulation AFR AF= 0.00207 (86/41556). AF 95% confidence interval is 0.00172. There are 0 homozygotes in gnomad4. There are 40 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FAM20A | NM_017565.4 | c.1381T>C | p.Leu461= | synonymous_variant | 11/11 | ENST00000592554.2 | NP_060035.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FAM20A | ENST00000592554.2 | c.1381T>C | p.Leu461= | synonymous_variant | 11/11 | 1 | NM_017565.4 | ENSP00000468308 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000598 AC: 91AN: 152170Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000171 AC: 42AN: 246212Hom.: 1 AF XY: 0.000150 AC XY: 20AN XY: 133186
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GnomAD4 exome AF: 0.0000671 AC: 98AN: 1460270Hom.: 0 Cov.: 35 AF XY: 0.0000620 AC XY: 45AN XY: 726256
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GnomAD4 genome AF: 0.000591 AC: 90AN: 152288Hom.: 0 Cov.: 32 AF XY: 0.000537 AC XY: 40AN XY: 74480
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 24, 2022 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at