X-154506852-C-G

Variant names:

• chrX-154506852-C-G
• rs781982533
• NM_021806.4:c.652G>C

Variant summary

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

The NM_021806.4(FAM3A):​c.652G>C​(p.Glu218Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000887 in 112,803 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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. E218K) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000089 (0 hom., 1 hem., cov: 24)
• Consequence: FAM3A NM_021806.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.36
• Publications: 2 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.652G>C	p.Glu218Gln	missense	Exon 9 of 9	NP_068578.2	P98173-1
	FAM3A	NM_001282311.2		c.694G>C	p.Glu232Gln	missense	Exon 10 of 10	NP_001269240.1	D3DWX8
	FAM3A	NM_001363822.2		c.673G>C	p.Glu225Gln	missense	Exon 10 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.652G>C	p.Glu218Gln	missense	Exon 9 of 9	ENSP00000416146.2	P98173-1
	FAM3A	ENST00000858761.1		c.742G>C	p.Glu248Gln	missense	Exon 9 of 9	ENSP00000528820.1
	FAM3A	ENST00000858759.1		c.700G>C	p.Glu234Gln	missense	Exon 9 of 9	ENSP00000528818.1

Frequencies

GnomAD3 genomes AF: 0.00000887 AC: 1 AN: 112803 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000279

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000887 AC: 1 AN: 112803 Hom.: 0 Cov.: 24 AF XY: 0.0000286 AC XY: 1 AN XY: 34991

African (AFR) AF: 0.00 AC: 0 AN: 31113

American (AMR) AF: 0.00 AC: 0 AN: 10711

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.000279 AC: 1 AN: 3578

South Asian (SAS) AF: 0.00 AC: 0 AN: 2803

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53201

Other (OTH) AF: 0.00 AC: 0 AN: 1520

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.089	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		7.4
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.25
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.59
MutPred		0.33		Loss of disorder (P = 0.1126)
MVP		0.33
MPC		0.90
ClinPred		0.98	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.58
gMVP		0.65
Mutation Taster		=80/20	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: rs781982533; hg19: chrX-153735183;