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GeneBe

7-193222-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

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 (★). Synonymous variant affecting the same amino acid position (i.e. R8R) has been classified 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

1
6
11

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FAM20CNM_020223.4 linkuse as main transcriptc.23G>A p.Arg8Gln missense_variant 1/10 ENST00000313766.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FAM20CENST00000313766.6 linkuse as main transcriptc.23G>A p.Arg8Gln missense_variant 1/101 NM_020223.4 P1Q8IXL6-1
ENST00000467050.1 linkuse as main transcriptn.233+726C>T intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
AF:
0.00132
AC:
198
AN:
149776
Hom.:
0
Cov.:
33
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:
23
AN:
118580
Hom.:
0
AF XY:
0.000139
AC XY:
9
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.:
2
Cov.:
30
AF XY:
0.0000571
AC XY:
37
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.:
0
Cov.:
33
AF XY:
0.00127
AC XY:
93
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.:
0
Bravo
AF:
0.00152
ESP6500AA
AF:
0.00505
AC:
14
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000466
AC:
10

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 submitterclinical testingInvitaeJan 05, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.25
Cadd
Uncertain
24
Dann
Uncertain
1.0
DEOGEN2
Benign
0.048
T
Eigen
Benign
0.027
Eigen_PC
Benign
0.098
FATHMM_MKL
Benign
0.36
N
LIST_S2
Uncertain
0.96
D
M_CAP
Pathogenic
0.86
D
MetaRNN
Benign
0.0091
T
MetaSVM
Benign
-0.61
T
MutationTaster
Benign
0.99
N
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-1.3
N
REVEL
Uncertain
0.36
Sift
Uncertain
0.0090
D
Sift4G
Uncertain
0.020
D
Polyphen
0.80
P
Vest4
0.11
MVP
0.54
MPC
0.73
ClinPred
0.058
T
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.

Other links and lift over

dbSNP: rs73251052; hg19: chr7-193222; COSMIC: COSV58233723; COSMIC: COSV58233723; API