3-194687031-A-G

Variant names:

• chr3-194687031-A-G
• rs1719434292
• NM_153690.5:c.205A>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_153690.5(FAM43A):​c.205A>G​(p.Thr69Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 8.60

Genes affected

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

LOC124909474 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.763

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM43A	NM_153690.5	c.205A>G	p.Thr69Ala	missense_variant	Exon 1 of 1	ENST00000329759.6	NP_710157.2
LOC124909474	XM_047449428.1	c.-778T>C		upstream_gene_variant			XP_047305384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM43A	ENST00000329759.6	c.205A>G	p.Thr69Ala	missense_variant	Exon 1 of 1	6	NM_153690.5	ENSP00000371397.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460280 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726222

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.0000166

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

Mar 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.205A>G (p.T69A) alteration is located in exon 1 (coding exon 1) of the FAM43A gene. This alteration results from a A to G substitution at nucleotide position 205, causing the threonine (T) at amino acid position 69 to be replaced by an alanine (A). 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	0.41
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.36	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.83
MutPred		0.39		Gain of catalytic residue at T69 (P = 0.0596);
MVP		0.59
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.33
gMVP		0.68

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: rs1719434292; hg19: chr3-194407760;