7-195685-T-C

Position:

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_020223.4(FAM20C):ā€‹c.737T>Cā€‹(p.Ile246Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000435 in 1,610,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000027 ( 0 hom. )

Consequence

FAM20C
NM_020223.4 missense

Scores

1
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.28
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.848

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FAM20CNM_020223.4 linkuse as main transcriptc.737T>C p.Ile246Thr missense_variant 2/10 ENST00000313766.6 NP_064608.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FAM20CENST00000313766.6 linkuse as main transcriptc.737T>C p.Ile246Thr missense_variant 2/101 NM_020223.4 ENSP00000322323 P1Q8IXL6-1
FAM20CENST00000471328.1 linkuse as main transcriptn.61T>C non_coding_transcript_exon_variant 1/23
FAM20CENST00000477004.1 linkuse as main transcriptn.218T>C non_coding_transcript_exon_variant 2/33

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152154
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1458788
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
725604
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152154
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000227

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 22, 2022The c.737T>C (p.I246T) alteration is located in exon 2 (coding exon 2) of the FAM20C gene. This alteration results from a T to C substitution at nucleotide position 737, causing the isoleucine (I) at amino acid position 246 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Uncertain
0.059
T
BayesDel_noAF
Benign
-0.15
CADD
Benign
19
DANN
Benign
0.96
DEOGEN2
Benign
0.062
T
Eigen
Benign
-0.16
Eigen_PC
Benign
-0.13
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.85
D
M_CAP
Uncertain
0.15
D
MetaRNN
Pathogenic
0.85
D
MetaSVM
Benign
-0.29
T
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.44
T
PROVEAN
Uncertain
-3.1
D
REVEL
Uncertain
0.49
Sift
Benign
0.032
D
Sift4G
Uncertain
0.036
D
Polyphen
0.038
B
Vest4
0.68
MutPred
0.66
Gain of disorder (P = 0.0101);
MVP
0.58
MPC
0.68
ClinPred
0.72
D
GERP RS
4.8
Varity_R
0.26
gMVP
0.50

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.

Other links and lift over

dbSNP: rs796051874; hg19: chr7-195685; API