X-154507440-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM3A	NM_021806.4	c.436G>C	p.Val146Leu	missense_variant	Exon 7 of 9	ENST00000447601.7	NP_068578.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM3A	ENST00000447601.7	c.436G>C	p.Val146Leu	missense_variant	Exon 7 of 9	1	NM_021806.4	ENSP00000416146.2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.436G>C (p.V146L) alteration is located in exon 7 (coding exon 7) of the FAM3A gene. This alteration results from a G to C substitution at nucleotide position 436, causing the valine (V) at amino acid position 146 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;.;T;T;T;.;.;T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	.;D;D;.;D;D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.66	D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;.;.;L;L;.;.;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-2.8	D;.;.;D;D;D;D;D
REVEL	Benign	0.26
Sift	Benign	0.031	D;.;.;D;D;T;T;D
Sift4G	Uncertain	0.0070	D;D;D;D;D;D;D;.
Polyphen		0.99	D;.;D;D;D;D;.;.
Vest4		0.59
MutPred		0.51		.;.;.;.;.;Loss of phosphorylation at T151 (P = 0.2387);.;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-153735771;