3-194686878-C-T

Variant names:

• chr3-194686878-C-T
• rs760764227
• NM_153690.5:c.52C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153690.5(FAM43A):​c.52C>T​(p.Arg18Trp) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R18G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FAM43A NM_153690.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 0 publications found

Genes affected

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

LOC124909474 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31211114).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153690.5. 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
	FAM43A	NM_153690.5	MANE Select	c.52C>T	p.Arg18Trp	missense	Exon 1 of 1	NP_710157.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM43A	ENST00000329759.6	TSL:6 MANE Select	c.52C>T	p.Arg18Trp	missense	Exon 1 of 1	ENSP00000371397.1	Q8N2R8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000451 AC: 1 AN: 221964 AF XY: 0.00000810

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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

African (AFR) AF: 0.00 AC: 0 AN: 31894

American (AMR) AF: 0.00 AC: 0 AN: 43250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25646

East Asian (EAS) AF: 0.00 AC: 0 AN: 37938

South Asian (SAS) AF: 0.0000354 AC: 3 AN: 84814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106984

Other (OTH) AF: 0.00 AC: 0 AN: 59742

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000834 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.0048	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.028	T
Eigen	Benign	0.042
Eigen_PC	Benign	0.026
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.78	T
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.31	T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.1
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.46
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.33
MutPred		0.36		Gain of solvent accessibility (P = 0.006)
MVP		0.45
ClinPred		0.76	D
GERP RS		3.1
Varity_R		0.17
gMVP		0.41
Mutation Taster		=79/21	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: rs760764227; hg19: chr3-194407607;