7-193245-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020223.4(FAM20C):c.46G>T(p.Val16Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00199 in 1,466,390 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 26 hom., cov: 33)

Exomes 𝑓: 0.00094 ( 20 hom. )

Consequence

FAM20C
NM_020223.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.00

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

lethal osteosclerotic bone dysplasia
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

FAM20C links:

ENSG00000240093 (HGNC:):

ENSG00000240093 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003346026).

BP6

Variant 7-193245-G-T is Benign according to our data. Variant chr7-193245-G-T is described in ClinVar as Benign. ClinVar VariationId is 193426.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0111 (1670/150092) while in subpopulation AFR AF = 0.0385 (1593/41344). AF 95% confidence interval is 0.037. There are 26 homozygotes in GnomAd4. There are 768 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM20C	NM_020223.4 link	c.46G>T	p.Val16Leu	missense_variant	Exon 1 of 10	ENST00000313766.6	NP_064608.2	Q8IXL6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM20C	ENST00000313766.6 link	c.46G>T	p.Val16Leu	missense_variant	Exon 1 of 10	1	NM_020223.4	ENSP00000322323.5		Q8IXL6-1

Frequencies

GnomAD3 genomes

AF:

0.0111

AC:

1672

AN:

149984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0387

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00318

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000178

Gnomad OTH

AF:

0.00776

GnomAD2 exomes

AF:

0.00148

AC:

172

AN:

116294

AF XY:

0.00112

show subpopulations

Gnomad AFR exome

AF:

0.0368

Gnomad AMR exome

AF:

0.00137

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000656

Gnomad OTH exome

AF:

0.000868

GnomAD4 exome

AF:

0.000943

AC:

1241

AN:

1316298

Hom.:

Cov.:

AF XY:

0.000808

AC XY:

525

AN XY:

649842

show subpopulations

African (AFR)

AF:

0.0394

AC:

1048

AN:

26580

American (AMR)

AF:

0.00143

AC:

AN:

32230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22214

East Asian (EAS)

AF:

0.00

AC:

AN:

29504

South Asian (SAS)

AF:

0.0000781

AC:

AN:

76776

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32294

Middle Eastern (MID)

AF:

0.000567

AC:

AN:

5288

European-Non Finnish (NFE)

AF:

0.0000250

AC:

AN:

1038096

Other (OTH)

AF:

0.00210

AC:

112

AN:

53316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

132

198

264

330

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0111

AC:

1670

AN:

150092

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

768

AN XY:

73292

show subpopulations

African (AFR)

AF:

0.0385

AC:

1593

AN:

41344

American (AMR)

AF:

0.00318

AC:

AN:

15118

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3442

East Asian (EAS)

AF:

0.00

AC:

AN:

5128

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9728

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000179

AC:

AN:

67218

Other (OTH)

AF:

0.00768

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

167

250

334

417

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00234

Hom.:

ESP6500AA

AF:

0.0332

AC:

ESP6500EA

AF:

0.000191

AC:

ExAC

AF:

0.00340

AC:

Asia WGS

AF:

0.00250

AC:

AN:

3212

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 28, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Feb 26, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0046

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0033

MetaSVM

Benign

-0.62

PhyloP100

3.0

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.75

REVEL

Benign

0.19

Sift

Benign

0.16

Sift4G

Benign

0.22

Polyphen

0.0020

Vest4

0.17

MutPred

0.35

Loss of MoRF binding (P = 0.0982);

MVP

0.37

MPC

0.47

ClinPred

0.0071

GERP RS

2.9

Varity_R

0.16

gMVP

0.66

Mutation Taster

=89/11

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over