1-20553122-A-G

Variant names:

• chr1-20553122-A-G
• rs1570357075
• NM_207334.3:c.149A>G

Variant summary

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

The NM_207334.3(FAM43B):​c.149A>G​(p.Glu50Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 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)
• Consequence: FAM43B NM_207334.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.43

Genes affected

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

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=0.16965762).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM43B	NM_207334.3	c.149A>G	p.Glu50Gly	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.149A>G	p.Glu50Gly	missense_variant	Exon 1 of 1	6	NM_207334.3	ENSP00000331397.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 21, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.149A>G (p.E50G) alteration is located in exon 1 (coding exon 1) of the FAM43B gene. This alteration results from a A to G substitution at nucleotide position 149, causing the glutamic acid (E) at amino acid position 50 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	Benign	0.17
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.094
Sift	Benign	0.13	T
Sift4G	Benign	0.26	T
Polyphen		0.19	B
Vest4		0.17
MutPred		0.24		Loss of solvent accessibility (P = 0.0062);
MVP		0.42
ClinPred		0.73	D
GERP RS		3.0
Varity_R		0.12
gMVP		0.56

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: rs1570357075; hg19: chr1-20879615;