3-194687633-A-C

Variant names:

• chr3-194687633-A-C
• rs146678404
• NM_153690.5:c.807A>C

Variant summary

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

The NM_153690.5(FAM43A):​c.807A>C​(p.Glu269Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: 7.1e-7 (0 hom.)
• Consequence: FAM43A NM_153690.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0380

Genes affected

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

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=0.11792374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM43A	NM_153690.5	c.807A>C	p.Glu269Asp	missense_variant	Exon 1 of 1	ENST00000329759.6	NP_710157.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM43A	ENST00000329759.6	c.807A>C	p.Glu269Asp	missense_variant	Exon 1 of 1	6	NM_153690.5	ENSP00000371397.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1412472 Hom.: 0 Cov.: 30 AF XY: 0.00000143 AC XY: 1 AN XY: 697914

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.807A>C (p.E269D) alteration is located in exon 1 (coding exon 1) of the FAM43A gene. This alteration results from a A to C substitution at nucleotide position 807, causing the glutamic acid (E) at amino acid position 269 to be replaced by an aspartic acid (D). 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	0.093
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0091	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.55	N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.19
Sift	Benign	0.11	T
Sift4G	Benign	0.55	T
Polyphen		0.84	P
Vest4		0.26
MutPred		0.19		Gain of loop (P = 0.024);
MVP		0.64
ClinPred		0.30	T
GERP RS		-1.8
Varity_R		0.043
gMVP		0.12

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: rs146678404; hg19: chr3-194408362;