Variant 17-68600260-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_017565.4(FAM20A):c.404+3G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 1,560,872 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 12 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 52 hom. )

Consequence

FAM20A
NM_017565.4 splice_region, intron

Scores

Splicing: ADA: 0.009446

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.838

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:):

LINC01482 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 17-68600260-C-T is Benign according to our data. Variant chr17-68600260-C-T is described in ClinVar as [Benign]. Clinvar id is 732806.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00423 (644/152190) while in subpopulation EAS AF= 0.0388 (199/5124). AF 95% confidence interval is 0.0344. There are 12 homozygotes in gnomad4. There are 430 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM20A	NM_017565.4 linkuse as main transcript	c.404+3G>A		splice_region_variant, intron_variant		ENST00000592554.2	NP_060035.2	Q96MK3L8B8N7Q8IYA5

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
FAM20A	ENST00000592554.2 linkuse as main transcript	c.404+3G>A	splice_region_variant, intron_variant	1	NM_017565.4	ENSP00000468308.1	Q96MK3
LINC01482	ENST00000587999.1 linkuse as main transcript	n.198+2114C>T	intron_variant	3
LINC01482	ENST00000589610.5 linkuse as main transcript	n.40+8382C>T	intron_variant	3
FAM20A	ENST00000590074.5 linkuse as main transcript	n.332+3G>A	splice_region_variant, intron_variant	2		ENSP00000464910.1	K7EIV7

Frequencies

GnomAD3 genomes

AF:

0.00423

AC:

643

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.0386

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0307

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00135

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00527

AC:

837

AN:

158706

Hom.:

AF XY:

0.00495

AC XY:

427

AN XY:

86258

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000357

Gnomad EAS exome

AF:

0.0285

Gnomad SAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.0254

Gnomad NFE exome

AF:

0.000895

Gnomad OTH exome

AF:

0.00323

GnomAD4 exome

AF:

0.00257

AC:

3621

AN:

1408682

Hom.:

Cov.:

AF XY:

0.00254

AC XY:

1768

AN XY:

696046

show subpopulations

Gnomad4 AFR exome

AF:

0.0000628

Gnomad4 AMR exome

AF:

0.0000265

Gnomad4 ASJ exome

AF:

0.000277

Gnomad4 EAS exome

AF:

0.0363

Gnomad4 SAS exome

AF:

0.00150

Gnomad4 FIN exome

AF:

0.0257

Gnomad4 NFE exome

AF:

0.000697

Gnomad4 OTH exome

AF:

0.00291

GnomAD4 genome

AF:

0.00423

AC:

644

AN:

152190

Hom.:

Cov.:

AF XY:

0.00578

AC XY:

430

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.0388

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.0307

Gnomad4 NFE

AF:

0.00135

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00215

Hom.:

Bravo

AF:

0.00166

Asia WGS

AF:

0.0150

AC:

AN:

3478

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

Jan 21, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

3.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0094

dbscSNV1_RF

Benign

0.14

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

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