NM_021806.4:c.393C>T

Variant names:

• chrX-154507483-G-A
• rs149966237
• NM_021806.4:c.393C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_021806.4(FAM3A):​c.393C>T​(p.Asn131Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00387 in 1,208,016 control chromosomes in the GnomAD database, including 5 homozygotes. There are 1,564 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (1 hom., 93 hem., cov: 23)
  • Exomes 𝑓: 0.0040 (4 hom. 1471 hem.)
• Consequence: FAM3A NM_021806.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.516
• 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: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant X-154507483-G-A is Benign according to our data. Variant chrX-154507483-G-A is described in ClinVar as Benign. ClinVar VariationId is 770831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.516 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 93 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.393C>T	p.Asn131Asn	synonymous	Exon 7 of 9	NP_068578.2	P98173-1
	FAM3A	NM_001282311.2		c.435C>T	p.Asn145Asn	synonymous	Exon 8 of 10	NP_001269240.1	D3DWX8
	FAM3A	NM_001363822.2		c.414C>T	p.Asn138Asn	synonymous	Exon 8 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.393C>T	p.Asn131Asn	synonymous	Exon 7 of 9	ENSP00000416146.2	P98173-1
	FAM3A	ENST00000858761.1		c.483C>T	p.Asn161Asn	synonymous	Exon 7 of 9	ENSP00000528820.1
	FAM3A	ENST00000858759.1		c.441C>T	p.Asn147Asn	synonymous	Exon 7 of 9	ENSP00000528818.1

Frequencies

GnomAD3 genomes AF: 0.00295 AC: 330 AN: 111924 Hom.: 1 Cov.: 23

Gnomad AFR AF: 0.000812

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00123

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00370

Gnomad FIN AF: 0.00114

Gnomad MID AF: 0.00418

Gnomad NFE AF: 0.00512

Gnomad OTH AF: 0.00132

GnomAD2 exomes AF: 0.00287 AC: 507 AN: 176785 AF XY: 0.00308

Gnomad AFR exome AF: 0.000631

Gnomad AMR exome AF: 0.00114

Gnomad ASJ exome AF: 0.000410

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00344

Gnomad NFE exome AF: 0.00446

Gnomad OTH exome AF: 0.00340

GnomAD4 exome AF: 0.00396 AC: 4345 AN: 1096043 Hom.: 4 Cov.: 31 AF XY: 0.00406 AC XY: 1471 AN XY: 361887

African (AFR) AF: 0.000379 AC: 10 AN: 26384

American (AMR) AF: 0.000967 AC: 34 AN: 35149

Ashkenazi Jewish (ASJ) AF: 0.000568 AC: 11 AN: 19371

East Asian (EAS) AF: 0.00 AC: 0 AN: 30194

South Asian (SAS) AF: 0.00285 AC: 154 AN: 53985

European-Finnish (FIN) AF: 0.00254 AC: 100 AN: 39412

Middle Eastern (MID) AF: 0.00150 AC: 6 AN: 4009

European-Non Finnish (NFE) AF: 0.00462 AC: 3884 AN: 841504

Other (OTH) AF: 0.00317 AC: 146 AN: 46035

GnomAD4 genome AF: 0.00295 AC: 330 AN: 111973 Hom.: 1 Cov.: 23 AF XY: 0.00272 AC XY: 93 AN XY: 34145

African (AFR) AF: 0.000810 AC: 25 AN: 30848

American (AMR) AF: 0.00123 AC: 13 AN: 10593

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3541

South Asian (SAS) AF: 0.00371 AC: 10 AN: 2695

European-Finnish (FIN) AF: 0.00114 AC: 7 AN: 6115

Middle Eastern (MID) AF: 0.00459 AC: 1 AN: 218

European-Non Finnish (NFE) AF: 0.00512 AC: 272 AN: 53099

Other (OTH) AF: 0.00131 AC: 2 AN: 1531

Alfa AF: 0.00422 Hom.: 29

Bravo AF: 0.00218

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	2.9
DANN	Benign	0.78
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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: rs149966237; hg19: chrX-153735814; COSMIC: COSV100453729; COSMIC: COSV100453729;