Variant chr8-123207416-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001394396.1(FAM83A):c.1033G>C(p.Gly345Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,458,118 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

FAM83A
NM_001394396.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.363

Variant links:

Genes affected

FAM83A (HGNC:28210): (family with sequence similarity 83 member A) Enables identical protein binding activity; phosphatidylinositol 3-kinase regulatory subunit binding activity; and protein kinase binding activity. Involved in cell population proliferation and epidermal growth factor receptor signaling pathway. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FAM83A links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04618138).

BP6

Variant 8-123207416-G-C is Benign according to our data. Variant chr8-123207416-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3092536.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM83A	NM_001394396.1 linkuse as main transcript	c.1033G>C	p.Gly345Arg	missense_variant	4/4	ENST00000690554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM83A	ENST00000690554.1 linkuse as main transcript	c.1033G>C	p.Gly345Arg	missense_variant	4/4		NM_001394396.1	P1	Q86UY5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1458118

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725480

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.63

DEOGEN2

Benign

0.020

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0064

LIST_S2

Benign

0.23

T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.046

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.051

Sift

Benign

0.30

T;T

Sift4G

Benign

0.79

T;T

Polyphen

0.0010

B;B

Vest4

0.046

MutPred

0.22

Gain of MoRF binding (P = 0.0186);.;

MVP

0.17

MPC

0.37

ClinPred

0.12

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.047

gMVP

0.20

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over