NM_021806.4:c.436G>C

Variant names:

• chrX-154507440-C-G
• NM_021806.4:c.436G>C

Variant summary

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

The NM_021806.4(FAM3A):​c.436G>C​(p.Val146Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: FAM3A NM_021806.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.42
• 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: 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.436G>C	p.Val146Leu	missense	Exon 7 of 9	NP_068578.2	P98173-1
	FAM3A	NM_001282311.2		c.478G>C	p.Val160Leu	missense	Exon 8 of 10	NP_001269240.1	D3DWX8
	FAM3A	NM_001363822.2		c.457G>C	p.Val153Leu	missense	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.436G>C	p.Val146Leu	missense	Exon 7 of 9	ENSP00000416146.2	P98173-1
	FAM3A	ENST00000858761.1		c.526G>C	p.Val176Leu	missense	Exon 7 of 9	ENSP00000528820.1
	FAM3A	ENST00000858759.1		c.484G>C	p.Val162Leu	missense	Exon 7 of 9	ENSP00000528818.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

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	Uncertain	0.52
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.4
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.26
Sift	Benign	0.031	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.99	D
Vest4		0.59
MutPred		0.51		Loss of phosphorylation at T151 (P = 0.2387)
MVP		0.26
MPC		0.70
ClinPred		0.98	D
GERP RS		4.4
Varity_R		0.71
gMVP		0.91
Mutation Taster		=69/31	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

hg19: chrX-153735771;