rs145815436

Variant names:

• chr17-18971517-C-A
• rs145815436
• NM_001039999.3:c.2314G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-18971517-C-A
• chr17-18971517-C-G
• chr17-18971517-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039999.3(FAM83G):​c.2314G>T​(p.Asp772Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D772N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM83G NM_001039999.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1822336).

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.2314G>T	p.Asp772Tyr	missense	Exon 6 of 6	NP_001035088.2	A6ND36-1
	SLC5A10	NM_001042450.4	MANE Select	c.846+299C>A		intron	N/A	NP_001035915.1	A0PJK1-1
	SLC5A10	NM_152351.6		c.846+299C>A		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.2314G>T	p.Asp772Tyr	missense	Exon 6 of 6	ENSP00000373647.5	A6ND36-1
	SLC5A10	ENST00000395645.4	TSL:1 MANE Select	c.846+299C>A		intron	N/A	ENSP00000379007.3	A0PJK1-1
	SLC5A10	ENST00000395643.6	TSL:1	c.765+299C>A		intron	N/A	ENSP00000379005.2	A0PJK1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.0088	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.5
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.17
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.031	D
Polyphen		0.98	D
Vest4		0.20
MutPred		0.20		Gain of phosphorylation at D772 (P = 0.0349)
MVP		0.48
MPC		0.73
ClinPred		0.70	D
GERP RS		3.0
Varity_R		0.11
gMVP		0.17

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: rs145815436; hg19: chr17-18874830;