NM_001039999.3:c.2425G>A

Variant names:

• chr17-18971406-C-T
• rs748816161
• NM_001039999.3:c.2425G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001039999.3(FAM83G):​c.2425G>A​(p.Asp809Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000806 in 1,613,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000086 (0 hom.)
• Consequence: FAM83G NM_001039999.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.63
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24244374).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039999.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM83G	NM_001039999.3	MANE Select	c.2425G>A	p.Asp809Asn	missense	Exon 6 of 6	NP_001035088.2	A6ND36-1
	SLC5A10	NM_001042450.4	MANE Select	c.846+188C>T		intron	N/A	NP_001035915.1	A0PJK1-1
	SLC5A10	NM_152351.6		c.846+188C>T		intron	N/A	NP_689564.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM83G	ENST00000388995.11	TSL:5 MANE Select	c.2425G>A	p.Asp809Asn	missense	Exon 6 of 6	ENSP00000373647.5	A6ND36-1
	SLC5A10	ENST00000395645.4	TSL:1 MANE Select	c.846+188C>T		intron	N/A	ENSP00000379007.3	A0PJK1-1
	SLC5A10	ENST00000395643.6	TSL:1	c.765+188C>T		intron	N/A	ENSP00000379005.2	A0PJK1-2

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152134 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000283 AC: 7 AN: 247752 AF XY: 0.0000297

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.000110

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000862 AC: 126 AN: 1461514 Hom.: 0 Cov.: 61 AF XY: 0.0000743 AC XY: 54 AN XY: 727096

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000344 AC: 9 AN: 26132

East Asian (EAS) AF: 0.000277 AC: 11 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000890 AC: 99 AN: 1111966

Other (OTH) AF: 0.0000994 AC: 6 AN: 60386

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152134 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74312

African (AFR) AF: 0.0000241 AC: 1 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000450 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Benign	0.13
Eigen_PC	Benign	-0.014
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.6
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.23
Sift	Benign	0.038	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.29
MutPred		0.15		Gain of methylation at K811 (P = 0.0765)
MVP		0.43
MPC		0.56
ClinPred		0.37	T
GERP RS		4.6
Varity_R		0.067
gMVP		0.12
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs748816161; hg19: chr17-18874719;