chr1-20553796-G-T

Variant names:

• chr1-20553796-G-T
• NM_207334.3:c.823G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_207334.3(FAM43B):​c.823G>T​(p.Ala275Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM43B NM_207334.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00800
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03976533).

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.823G>T	p.Ala275Ser	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.823G>T	p.Ala275Ser	missense	Exon 1 of 1	ENSP00000331397.4	Q6ZT52

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1325508 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 653894

African (AFR) AF: 0.00 AC: 0 AN: 26690

American (AMR) AF: 0.00 AC: 0 AN: 29452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22682

East Asian (EAS) AF: 0.00 AC: 0 AN: 27728

South Asian (SAS) AF: 0.00 AC: 0 AN: 74270

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3968

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1041226

Other (OTH) AF: 0.00 AC: 0 AN: 53944

GnomAD4 genome Cov.: 33

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	Benign	0.079
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.7
DANN	Benign	0.76
DEOGEN2	Benign	0.0085	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.0080
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.0090
Sift	Benign	0.70	T
Sift4G	Benign	0.78	T
Polyphen		0.0030	B
Vest4		0.065
MutPred		0.19		Gain of phosphorylation at A275 (P = 6e-04)
MVP		0.040
ClinPred		0.041	T
GERP RS		-0.19
Varity_R		0.045
gMVP		0.14
Mutation Taster		=96/4	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: chr1-20880289;