rs11649763

chr17-68565062-T-Cchr17-68565062-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017565.4(FAM20A):c.405-9319A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,010 control chromosomes in the GnomAD database, including 2,270 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2270 hom., cov: 31)
• Consequence: FAM20A NM_017565.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM20A	NM_017565.4	c.405-9319A>G		intron_variant		ENST00000592554.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM20A	ENST00000592554.2	c.405-9319A>G		intron_variant		1	NM_017565.4	P1
	ENST00000589826.1	n.76+7471T>C		intron_variant, non_coding_transcript_variant		2
FAM20A	ENST00000590074.5	c.*178-9319A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24891 AN: 151892 Hom.: 2262 Cov.: 31

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.175

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.164 AC: 24931 AN: 152010 Hom.: 2270 Cov.: 31 AF XY: 0.165 AC XY: 12290 AN XY: 74296

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.174

Alfa AF: 0.165 Hom.: 654

Bravo AF: 0.161

Asia WGS AF: 0.221 AC: 765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.46
Dann	Benign	0.63

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

LitVar

Other links and lift over

dbSNP: rs11649763; hg19: chr17-66561203;