rs781982533

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-154506852-C-T
• chrX-154506852-C-G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_021806.4(FAM3A):​c.652G>A​(p.Glu218Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000014 in 1,210,634 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000044 (0 hom., 1 hem., cov: 24)
  • Exomes 𝑓: 0.000011 (0 hom. 5 hem.)
• Consequence: FAM3A NM_021806.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.40340155).
• BS2: High Hemizygotes in GnomAdExome4 at 5 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.652G>A	p.Glu218Lys	missense	Exon 9 of 9	NP_068578.2	P98173-1
	FAM3A	NM_001282311.2		c.694G>A	p.Glu232Lys	missense	Exon 10 of 10	NP_001269240.1	D3DWX8
	FAM3A	NM_001363822.2		c.673G>A	p.Glu225Lys	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>A	p.Glu218Lys	missense	Exon 9 of 9	ENSP00000416146.2	P98173-1
	FAM3A	ENST00000858761.1		c.742G>A	p.Glu248Lys	missense	Exon 9 of 9	ENSP00000528820.1
	FAM3A	ENST00000858759.1		c.700G>A	p.Glu234Lys	missense	Exon 9 of 9	ENSP00000528818.1

Frequencies

GnomAD3 genomes AF: 0.0000443 AC: 5 AN: 112803 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000187

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: 0.0000564

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000219 AC: 4 AN: 182405 AF XY: 0.0000297

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000370

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 12 AN: 1097777 Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 5 AN XY: 363175

African (AFR) AF: 0.00 AC: 0 AN: 26393

American (AMR) AF: 0.0000284 AC: 1 AN: 35198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19375

East Asian (EAS) AF: 0.00 AC: 0 AN: 30199

South Asian (SAS) AF: 0.00 AC: 0 AN: 54123

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.0000131 AC: 11 AN: 841795

Other (OTH) AF: 0.00 AC: 0 AN: 46072

GnomAD4 genome AF: 0.0000443 AC: 5 AN: 112857 Hom.: 0 Cov.: 24 AF XY: 0.0000285 AC XY: 1 AN XY: 35055

African (AFR) AF: 0.00 AC: 0 AN: 31182

American (AMR) AF: 0.000186 AC: 2 AN: 10724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3567

South Asian (SAS) AF: 0.00 AC: 0 AN: 2795

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.0000564 AC: 3 AN: 53194

Other (OTH) AF: 0.00 AC: 0 AN: 1539

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000756

ExAC AF: 0.0000494 AC: 6

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	Pathogenic	0.93
BayesDel_addAF	Benign	-0.0061	T
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.26	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		7.4
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.26
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.050	T
Polyphen		0.94	P
Vest4		0.72
MutPred		0.42		Gain of MoRF binding (P = 0.0109)
MVP		0.36
MPC		0.84
ClinPred		0.82	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.60
gMVP		0.83
Mutation Taster		=99/1	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;