Variant 1-231040166-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198552.3(FAM89A):c.46G>C(p.Val16Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000212 in 1,196,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

FAM89A
NM_198552.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74

Variant links:

Genes affected

FAM89A (HGNC:25057): (family with sequence similarity 89 member A)

FAM89A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05626583).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM89A	NM_198552.3 linkuse as main transcript	c.46G>C	p.Val16Leu	missense_variant	1/2	ENST00000366654.5	NP_940954.1	Q96GI7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM89A	ENST00000366654.5 linkuse as main transcript	c.46G>C	p.Val16Leu	missense_variant	1/2	1	NM_198552.3	ENSP00000355614.4		Q96GI7

Frequencies

GnomAD3 genomes

AF:

0.000182

AC:

AN:

147974

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000736

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000670

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000331

Gnomad OTH

AF:

0.000491

GnomAD3 exomes

AF:

0.0000919

AC:

AN:

10878

Hom.:

AF XY:

0.00

AC XY:

AN XY:

7226

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000192

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000217

AC:

227

AN:

1048230

Hom.:

Cov.:

AF XY:

0.000214

AC XY:

107

AN XY:

499936

show subpopulations

Gnomad4 AFR exome

AF:

0.0000476

Gnomad4 AMR exome

AF:

0.000132

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:

0.000247

Gnomad4 OTH exome

AF:

0.0000745

GnomAD4 genome

AF:

0.000182

AC:

AN:

148082

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

AN XY:

72246

show subpopulations

Gnomad4 AFR

AF:

0.0000734

Gnomad4 AMR

AF:

0.0000669

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000331

Gnomad4 OTH

AF:

0.000485

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000151

ExAC

AF:

0.000137

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2024

The c.46G>C (p.V16L) alteration is located in exon 1 (coding exon 1) of the FAM89A gene. This alteration results from a G to C substitution at nucleotide position 46, causing the valine (V) at amino acid position 16 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.014

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.39

M_CAP

Benign

0.021

MetaRNN

Benign

0.056

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.24

REVEL

Benign

0.0070

Sift

Benign

0.17

Sift4G

Benign

0.13

Polyphen

0.0050

Vest4

0.13

MVP

0.030

MPC

0.28

ClinPred

0.061

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.078

gMVP

0.19

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over