NM_207334.3:c.965G>C

Variant names:

• chr1-20553938-G-C
• rs2052162756
• NM_207334.3:c.965G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207334.3(FAM43B):​c.965G>C​(p.Arg322Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000922 in 1,084,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R322K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.2e-7 (0 hom.)
• Consequence: FAM43B NM_207334.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15234685).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207334.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM43B	NM_207334.3	MANE Select	c.965G>C	p.Arg322Thr	missense	Exon 1 of 1	NP_997217.1	Q6ZT52

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM43B	ENST00000332947.6	TSL:6 MANE Select	c.965G>C	p.Arg322Thr	missense	Exon 1 of 1	ENSP00000331397.4	Q6ZT52

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.22e-7 AC: 1 AN: 1084862 Hom.: 0 Cov.: 31 AF XY: 0.00000193 AC XY: 1 AN XY: 519082

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22054

American (AMR) AF: 0.00 AC: 0 AN: 7578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13016

East Asian (EAS) AF: 0.00 AC: 0 AN: 24382

South Asian (SAS) AF: 0.00 AC: 0 AN: 21724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2832

European-Non Finnish (NFE) AF: 0.00000108 AC: 1 AN: 926330

Other (OTH) AF: 0.00 AC: 0 AN: 42764

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Benign	0.86
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.56	T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.5
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.029
Sift	Benign	0.056	T
Sift4G	Benign	0.54	T
Polyphen		0.32	B
Vest4		0.23
MutPred		0.18		Gain of phosphorylation at R322 (P = 0.0166)
MVP		0.48
ClinPred		0.14	T
GERP RS		2.4
Varity_R		0.11
gMVP		0.26
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs2052162756; hg19: chr1-20880431;