NM_207334.3:c.737A>T

Variant names:

• chr1-20553710-A-T
• NM_207334.3:c.737A>T

Variant summary

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

The NM_207334.3(FAM43B):​c.737A>T​(p.Tyr246Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000077 in 1,298,300 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: FAM43B NM_207334.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.96
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.737A>T	p.Tyr246Phe	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.737A>T	p.Tyr246Phe	missense	Exon 1 of 1	ENSP00000331397.4	Q6ZT52

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.70e-7 AC: 1 AN: 1298300 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 640022

African (AFR) AF: 0.00 AC: 0 AN: 26052

American (AMR) AF: 0.00 AC: 0 AN: 26646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21976

East Asian (EAS) AF: 0.00 AC: 0 AN: 26224

South Asian (SAS) AF: 0.00 AC: 0 AN: 72066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39082

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3720

European-Non Finnish (NFE) AF: 9.71e-7 AC: 1 AN: 1030068

Other (OTH) AF: 0.00 AC: 0 AN: 52466

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	0.0014	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.039	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.62	T
M_CAP	Pathogenic	0.34	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.0	L
PhyloP100		6.0
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.23
Sift	Benign	0.20	T
Sift4G	Benign	0.23	T
Polyphen		1.0	D
Vest4		0.51
MutPred		0.40		Loss of phosphorylation at Y246 (P = 0.0172)
MVP		0.25
ClinPred		0.90	D
GERP RS		3.5
Varity_R		0.30
gMVP		0.31
Mutation Taster		=82/18	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

hg19: chr1-20880203;