NM_017565.4:c.405-9319A>G

Variant names:

• chr17-68565062-T-C
• rs11649763
• NM_017565.4:c.405-9319A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• amelogenesis imperfecta type 1G

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics

ENSG00000267461 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FAM20A	NM_017565.4	c.405-9319A>G		intron_variant	Intron 1 of 10	ENST00000592554.2	NP_060035.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM20A	ENST00000592554.2	c.405-9319A>G		intron_variant	Intron 1 of 10	1	NM_017565.4	ENSP00000468308.1
ENSG00000267461	ENST00000589826.1	n.76+7471T>C		intron_variant	Intron 1 of 2	2
FAM20A	ENST00000590074.5	n.*178-9319A>G		intron_variant	Intron 2 of 11	2		ENSP00000464910.1

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

African (AFR) AF: 0.135 AC: 5604 AN: 41480

American (AMR) AF: 0.138 AC: 2102 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 553 AN: 3466

East Asian (EAS) AF: 0.340 AC: 1751 AN: 5146

South Asian (SAS) AF: 0.210 AC: 1009 AN: 4806

European-Finnish (FIN) AF: 0.146 AC: 1546 AN: 10568

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11806 AN: 67954

Other (OTH) AF: 0.174 AC: 367 AN: 2112

Alfa AF: 0.164 Hom.: 796

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
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11649763; hg19: chr17-66561203;