Variant 7-193222-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_020223.4(FAM20C):c.23G>A(p.Arg8Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000239 in 1,462,028 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 2 hom. )

Consequence

FAM20C
NM_020223.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.24

Variant links:

Genes affected

FAM20C (HGNC:22140): (FAM20C golgi associated secretory pathway kinase) This gene encodes a member of the family of secreted protein kinases. The encoded protein binds calcium and phosphorylates proteins involved in bone mineralization. Mutations in this gene are associated with the autosomal recessive disorder Raine syndrome. [provided by RefSeq, Apr 2014]

FAM20C links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009070009).

BP6

Variant 7-193222-G-A is Benign according to our data. Variant chr7-193222-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 724470.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-193222-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00133 (199/149882) while in subpopulation AFR AF= 0.00465 (192/41304). AF 95% confidence interval is 0.00411. There are 0 homozygotes in gnomad4. There are 93 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM20C	NM_020223.4 linkuse as main transcript	c.23G>A	p.Arg8Gln	missense_variant	1/10	ENST00000313766.6	NP_064608.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM20C	ENST00000313766.6 linkuse as main transcript	c.23G>A	p.Arg8Gln	missense_variant	1/10	1	NM_020223.4	ENSP00000322323	P1	Q8IXL6-1
	ENST00000467050.1 linkuse as main transcript	n.233+726C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00132

AC:

198

AN:

149776

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00464

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000199

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00146

GnomAD3 exomes

AF:

0.000194

AC:

AN:

118580

Hom.:

AF XY:

0.000139

AC XY:

AN XY:

64854

show subpopulations

Gnomad AFR exome

AF:

0.00457

Gnomad AMR exome

AF:

0.000225

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000114

AC:

150

AN:

1312146

Hom.:

Cov.:

AF XY:

0.0000571

AC XY:

AN XY:

648048

show subpopulations

Gnomad4 AFR exome

AF:

0.00480

Gnomad4 AMR exome

AF:

0.000216

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000130

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000290

Gnomad4 OTH exome

AF:

0.000208

GnomAD4 genome

AF:

0.00133

AC:

199

AN:

149882

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

AN XY:

73166

show subpopulations

Gnomad4 AFR

AF:

0.00465

Gnomad4 AMR

AF:

0.000199

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000149

Gnomad4 OTH

AF:

0.00144

Alfa

AF:

0.000662

Hom.:

Bravo

AF:

0.00152

ESP6500AA

AF:

0.00505

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000466

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 05, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.048

Eigen

Benign

0.027

Eigen_PC

Benign

0.098

FATHMM_MKL

Benign

0.36

LIST_S2

Uncertain

0.96

M_CAP

Pathogenic

0.86

MetaRNN

Benign

0.0091

MetaSVM

Benign

-0.61

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.36

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.020

Polyphen

0.80

Vest4

0.11

MVP

0.54

MPC

0.73

ClinPred

0.058

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.14

gMVP

0.49

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

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