rs929283877

Variant names:

• chrX-154508586-T-C
• rs929283877
• NM_021806.4:c.163A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-154508586-T-C
• chrX-154508586-T-G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_021806.4(FAM3A):​c.163A>G​(p.Arg55Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000084 in 1,190,231 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., 2 hem., cov: 25)
  • Exomes 𝑓: 0.0000037 (0 hom. 1 hem.)
• Consequence: FAM3A NM_021806.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.96
• Publications: 0 publications found

Genes affected

FAM3A (HGNC:13749): (FAM3 metabolism regulating signaling molecule A) This gene encodes a cytokine-like protein. The expression of this gene may be regulated by peroxisome proliferator-activated receptor gamma, and the encoded protein may be involved in the regulation of glucose and lipid metabolism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16408116).
• BS2: High Hemizygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021806.4. 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
	FAM3A	NM_021806.4	MANE Select	c.163A>G	p.Arg55Gly	missense	Exon 4 of 9	NP_068578.2	P98173-1
	FAM3A	NM_001282311.2		c.205A>G	p.Arg69Gly	missense	Exon 5 of 10	NP_001269240.1	D3DWX8
	FAM3A	NM_001363822.2		c.163A>G	p.Arg55Gly	missense	Exon 5 of 10	NP_001350751.1	Q5HY75

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM3A	ENST00000447601.7	TSL:1 MANE Select	c.163A>G	p.Arg55Gly	missense	Exon 4 of 9	ENSP00000416146.2	P98173-1
	FAM3A	ENST00000858761.1		c.163A>G	p.Arg55Gly	missense	Exon 4 of 9	ENSP00000528820.1
	FAM3A	ENST00000858759.1		c.211A>G	p.Arg71Gly	missense	Exon 4 of 9	ENSP00000528818.1

Frequencies

GnomAD3 genomes AF: 0.0000530 AC: 6 AN: 113138 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000465

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: 0.000654

GnomAD2 exomes AF: 0.00 AC: 0 AN: 143062 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000371 AC: 4 AN: 1077093 Hom.: 0 Cov.: 31 AF XY: 0.00000286 AC XY: 1 AN XY: 349807

African (AFR) AF: 0.00 AC: 0 AN: 26099

American (AMR) AF: 0.00 AC: 0 AN: 31924

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18888

East Asian (EAS) AF: 0.00 AC: 0 AN: 29374

South Asian (SAS) AF: 0.00 AC: 0 AN: 51363

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38676

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4108

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 831337

Other (OTH) AF: 0.0000883 AC: 4 AN: 45324

GnomAD4 genome AF: 0.0000530 AC: 6 AN: 113138 Hom.: 0 Cov.: 25 AF XY: 0.0000567 AC XY: 2 AN XY: 35276

African (AFR) AF: 0.00 AC: 0 AN: 31208

American (AMR) AF: 0.000465 AC: 5 AN: 10756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2656

East Asian (EAS) AF: 0.00 AC: 0 AN: 3601

South Asian (SAS) AF: 0.00 AC: 0 AN: 2841

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6305

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53319

Other (OTH) AF: 0.000654 AC: 1 AN: 1529

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000756

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	0.16
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.069	T
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.0
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.12
Sift	Benign	0.38	T
Sift4G	Benign	0.37	T
Polyphen		0.23	B
Vest4		0.41
MutPred		0.34		Gain of ubiquitination at K58 (P = 0.0396)
MVP		0.20
MPC		0.54
ClinPred		0.61	D
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.68
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

dbSNP: rs929283877; hg19: chrX-153736917;