NM_207334.3:c.946C>T

Variant names:

• chr1-20553919-C-T
• rs1570357818
• NM_207334.3:c.946C>T

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.946C>T​(p.Arg316Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,101,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. R316S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: FAM43B NM_207334.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• 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=0.23860332).

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.946C>T	p.Arg316Cys	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.946C>T	p.Arg316Cys	missense	Exon 1 of 1	ENSP00000331397.4	Q6ZT52

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000136 AC: 15 AN: 1101382 Hom.: 0 Cov.: 30 AF XY: 0.00000756 AC XY: 4 AN XY: 528826

African (AFR) AF: 0.00 AC: 0 AN: 22310

American (AMR) AF: 0.00 AC: 0 AN: 7838

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13368

East Asian (EAS) AF: 0.00 AC: 0 AN: 25030

South Asian (SAS) AF: 0.00 AC: 0 AN: 24012

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2886

European-Non Finnish (NFE) AF: 0.0000160 AC: 15 AN: 936146

Other (OTH) AF: 0.00 AC: 0 AN: 43666

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.041
Eigen_PC	Benign	-0.045
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.60	T
M_CAP	Pathogenic	0.48	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.024
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.077
Sift	Uncertain	0.010	D
Sift4G	Benign	0.092	T
Polyphen		0.99	D
Vest4		0.099
MutPred		0.27		Gain of catalytic residue at W317 (P = 5e-04)
MVP		0.44
ClinPred		0.59	D
GERP RS		3.2
Varity_R		0.10
gMVP		0.22
Mutation Taster		=72/28	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: rs1570357818; hg19: chr1-20880412;