NM_001010872.3:c.115G>C

Variant names:

• chr6-54870361-G-C
• rs773921453
• NM_001010872.3:c.115G>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001010872.3(FAM83B):​c.115G>C​(p.Gly39Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/22 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: FAM83B NM_001010872.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.92
• Publications: 0 publications found

Genes affected

FAM83B (HGNC:21357): (family with sequence similarity 83 member B) Enables epidermal growth factor receptor binding activity; phosphatidylinositol 3-kinase binding activity; and protein kinase binding activity. Involved in cell population proliferation and epidermal growth factor receptor signaling pathway. Located in cytoplasm and membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.98

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010872.3. 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
	FAM83B	NM_001010872.3	MANE Select	c.115G>C	p.Gly39Arg	missense	Exon 2 of 5	NP_001010872.1	Q5T0W9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM83B	ENST00000306858.8	TSL:1 MANE Select	c.115G>C	p.Gly39Arg	missense	Exon 2 of 5	ENSP00000304078.7	Q5T0W9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461758 Hom.: 0 Cov.: 34 AF XY: 0.00000550 AC XY: 4 AN XY: 727196

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111930

Other (OTH) AF: 0.00 AC: 0 AN: 60388

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	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.28	T
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.061	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Benign	-0.57	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		9.9
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-6.6	D
REVEL	Pathogenic	0.67
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.89		Loss of catalytic residue at G39 (P = 0.1472)
MVP		0.73
MPC		0.35
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.91
gMVP		0.85
Mutation Taster		=54/46	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: rs773921453; hg19: chr6-54735159;