Genetic Variant FAM83G:p.Gly784Arg (chr17-18971481-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001039999.3(FAM83G):c.2350G>C(p.Gly784Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,892 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

FAM83G
NM_001039999.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.92

Variant links:

Genes affected

FAM83G (HGNC:32554): (family with sequence similarity 83 member G) Predicted to enable protein kinase binding activity. Involved in BMP signaling pathway. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FAM83G links:

SLC5A10 (HGNC:23155): (solute carrier family 5 member 10) This gene is a member of the sodium/glucose transporter family. Members of this family are sodium-dependent transporters and can be divided into two subfamilies based on sequence homology, one that co-transports sugars and the second that transports molecules such as ascorbate, choline, iodide, lipoate, monocaroboxylates, and pantothenate. The protein encoded by this gene has the highest affinity for mannose and has been reported to be most highly expressed in the kidney. This protein may function as a kidney-specific, sodium-dependent mannose and fructose co-transporter. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

SLC5A10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM83G	NM_001039999.3 link	c.2350G>C	p.Gly784Arg	missense_variant	Exon 6 of 6	ENST00000388995.11	NP_001035088.2	A6ND36-1
SLC5A10	NM_001042450.4 link	c.846+263C>G		intron_variant	Intron 8 of 14	ENST00000395645.4	NP_001035915.1	A0PJK1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM83G	ENST00000388995.11 link	c.2350G>C	p.Gly784Arg	missense_variant	Exon 6 of 6	5	NM_001039999.3	ENSP00000373647.5		A6ND36-1
SLC5A10	ENST00000395645.4 link	c.846+263C>G		intron_variant	Intron 8 of 14	1	NM_001042450.4	ENSP00000379007.3		A0PJK1-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000808

AC:

AN:

247492

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134462

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461700

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.033

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

T;T

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.81

.;T

M_CAP

Benign

0.078

MetaRNN

Uncertain

0.50

D;D

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.66

N;N

REVEL

Benign

0.11

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.97

D;D

Vest4

0.67

MutPred

0.22

Gain of MoRF binding (P = 0.0168);Gain of MoRF binding (P = 0.0168);

MVP

0.52

MPC

0.80

ClinPred

0.92

GERP RS

4.4

Varity_R

0.30

gMVP

0.41

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over