3-194686878-C-G

Position:

• chr3-194686878-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153690.5(FAM43A):​c.52C>G​(p.Arg18Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,445,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FAM43A NM_153690.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.14

Genes affected

FAM43A (HGNC:26888): (family with sequence similarity 43 member A)

LOC124909474 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19330928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM43A	NM_153690.5	c.52C>G	p.Arg18Gly	missense_variant	1/1	ENST00000329759.6
LOC124909474	XM_047449428.1	c.-625G>C		5_prime_UTR_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM43A	ENST00000329759.6	c.52C>G	p.Arg18Gly	missense_variant	1/1		NM_153690.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000180 AC: 4 AN: 221964 Hom.: 0 AF XY: 0.0000324 AC XY: 4 AN XY: 123448

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000123

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1445950 Hom.: 0 Cov.: 31 AF XY: 0.00000417 AC XY: 3 AN XY: 719404

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000694

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000113

ExAC AF: 0.00000834 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2023

The c.52C>G (p.R18G) alteration is located in exon 1 (coding exon 1) of the FAM43A gene. This alteration results from a C to G substitution at nucleotide position 52, causing the arginine (R) at amino acid position 18 to be replaced by a glycine (G). 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	Benign	0.18
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.088
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.63	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	0.94	D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.53	N
REVEL	Uncertain	0.40
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.022	D
Polyphen		0.87	P
Vest4		0.26
MutPred		0.19		Gain of relative solvent accessibility (P = 0.0166);
MVP		0.53
ClinPred		0.39	T
GERP RS		3.1
Varity_R		0.32
gMVP		0.43

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

LitVar

Other links and lift over

dbSNP: rs760764227; hg19: chr3-194407607;