chr7-259906-G-A

Position:

chr7-259906-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The ENST00000313766.6(FAM20C):c.1681G>A(p.Val561Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00456 in 1,535,438 control chromosomes in the GnomAD database, including 254 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V561E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0043 ( 25 hom., cov: 35)

Exomes 𝑓: 0.0046 ( 229 hom. )

Consequence

FAM20C
ENST00000313766.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.51

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

PM1

In a region_of_interest Kinase domain (size 211) in uniprot entity FA20C_HUMAN there are 19 pathogenic changes around while only 4 benign (83%) in ENST00000313766.6

BP4

Computational evidence support a benign effect (MetaRNN=0.0035103261).

BP6

Variant 7-259906-G-A is Benign according to our data. Variant chr7-259906-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 193729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-259906-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM20C	NM_020223.4 linkuse as main transcript	c.1681G>A	p.Val561Met	missense_variant	10/10	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.1681G>A	p.Val561Met	missense_variant	10/10	1	NM_020223.4	ENSP00000322323	P1	Q8IXL6-1
FAM20C	ENST00000515795.1 linkuse as main transcript	n.1338G>A		non_coding_transcript_exon_variant	7/7	1

Frequencies

GnomAD3 genomes

AF:

0.00428

AC:

651

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0679

Gnomad SAS

AF:

0.0426

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.0117

AC:

1646

AN:

140488

Hom.:

AF XY:

0.0134

AC XY:

1014

AN XY:

75466

show subpopulations

Gnomad AFR exome

AF:

0.000404

Gnomad AMR exome

AF:

0.000244

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0654

Gnomad SAS exome

AF:

0.0387

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000611

Gnomad OTH exome

AF:

0.00764

GnomAD4 exome

AF:

0.00459

AC:

6355

AN:

1383076

Hom.:

229

Cov.:

AF XY:

0.00556

AC XY:

3797

AN XY:

682332

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.000308

Gnomad4 ASJ exome

AF:

0.0000397

Gnomad4 EAS exome

AF:

0.0720

Gnomad4 SAS exome

AF:

0.0372

Gnomad4 FIN exome

AF:

0.0000587

Gnomad4 NFE exome

AF:

0.000266

Gnomad4 OTH exome

AF:

0.00800

GnomAD4 genome

AF:

0.00428

AC:

652

AN:

152362

Hom.:

Cov.:

AF XY:

0.00533

AC XY:

397

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0673

Gnomad4 SAS

AF:

0.0429

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00408

Hom.:

Bravo

AF:

0.00379

ESP6500AA

AF:

0.00145

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.0154

AC:

325

Asia WGS

AF:

0.0560

AC:

194

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 21, 2015	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Oct 20, 2014

- -

Lethal osteosclerotic bone dysplasia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 29, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.23

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0035

MetaSVM

Benign

-0.87

MutationTaster

Benign

0.61

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.3

REVEL

Benign

0.22

Sift

Benign

0.069

Sift4G

Benign

0.087

Polyphen

0.61

Vest4

0.12

MPC

0.95

ClinPred

0.025

GERP RS

-0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.37

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