1-20553488-T-G

Variant names:

• chr1-20553488-T-G
• rs2052155271
• NM_207334.3:c.515T>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_207334.3(FAM43B):​c.515T>G​(p.Val172Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000032 in 1,250,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: FAM43B NM_207334.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.83

Genes affected

FAM43B (HGNC:31791): (family with sequence similarity 43 member B)

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.855

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM43B	NM_207334.3	c.515T>G	p.Val172Gly	missense_variant	Exon 1 of 1	ENST00000332947.6	NP_997217.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM43B	ENST00000332947.6	c.515T>G	p.Val172Gly	missense_variant	Exon 1 of 1	6	NM_207334.3	ENSP00000331397.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000320 AC: 4 AN: 1250616 Hom.: 0 Cov.: 31 AF XY: 0.00000327 AC XY: 2 AN XY: 612064

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: 0.00000391

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.515T>G (p.V172G) alteration is located in exon 1 (coding exon 1) of the FAM43B gene. This alteration results from a T to G substitution at nucleotide position 515, causing the valine (V) at amino acid position 172 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	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.79	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Pathogenic	0.95	D
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.34
Sift	Benign	0.095	T
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.57
MutPred		0.72		Gain of helix (P = 0.0078);
MVP		0.63
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.54
gMVP		0.58

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: rs2052155271; hg19: chr1-20879981;