1-20553725-G-C

Variant names:

• chr1-20553725-G-C
• NM_207334.3:c.752G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_207334.3(FAM43B):​c.752G>C​(p.Ser251Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000153 in 1,307,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign 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: 0.0000015 (0 hom.)
• Consequence: FAM43B NM_207334.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.718

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034482032).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM43B	NM_207334.3	c.752G>C	p.Ser251Thr	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.752G>C	p.Ser251Thr	missense_variant	Exon 1 of 1	6	NM_207334.3	ENSP00000331397.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000153 AC: 2 AN: 1307994 Hom.: 0 Cov.: 31 AF XY: 0.00000310 AC XY: 2 AN XY: 644814

Gnomad4 AFR exome AF: 0.0000382

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: 9.67e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.752G>C (p.S251T) alteration is located in exon 1 (coding exon 1) of the FAM43B gene. This alteration results from a G to C substitution at nucleotide position 752, causing the serine (S) at amino acid position 251 to be replaced by a threonine (T). 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	0.073
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.86
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.14	T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	0.29	N
REVEL	Benign	0.034
Sift	Benign	0.13	T
Sift4G	Benign	0.18	T
Polyphen		0.0	B
Vest4		0.072
MutPred		0.17		Gain of glycosylation at S251 (P = 0.0318);
MVP		0.15
ClinPred		0.026	T
GERP RS		1.5
Varity_R		0.080
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-20880218;