Variant 1-231020038-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_198552.3(FAM89A):c.380C>G(p.Ala127Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,614,114 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00088 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 4 hom. )

Consequence

FAM89A
NM_198552.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.08

Variant links:

Genes affected

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

FAM89A links:

FAM89A (HGNC:):

FAM89A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03095135).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM89A	NM_198552.3 linkuse as main transcript	c.380C>G	p.Ala127Gly	missense_variant	2/2	ENST00000366654.5	NP_940954.1	Q96GI7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FAM89A	ENST00000366654.5 linkuse as main transcript	c.380C>G	p.Ala127Gly	missense_variant	2/2	1	NM_198552.3	ENSP00000355614.4	Q96GI7
FAM89A	ENST00000466258.1 linkuse as main transcript	n.363C>G		non_coding_transcript_exon_variant	2/2	3
FAM89A	ENST00000494111.1 linkuse as main transcript	n.714C>G		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes

AF:

0.000881

AC:

134

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00162

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000852

AC:

214

AN:

251278

Hom.:

AF XY:

0.000847

AC XY:

115

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00173

Gnomad OTH exome

AF:

0.000651

GnomAD4 exome

AF:

0.00169

AC:

2474

AN:

1461816

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

1161

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00214

Gnomad4 OTH exome

AF:

0.000844

GnomAD4 genome

AF:

0.000880

AC:

134

AN:

152298

Hom.:

Cov.:

AF XY:

0.000739

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00162

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00161

Hom.:

Bravo

AF:

0.000918

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.000774

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

Apr 06, 2022

The c.380C>G (p.A127G) alteration is located in exon 2 (coding exon 2) of the FAM89A gene. This alteration results from a C to G substitution at nucleotide position 380, causing the alanine (A) at amino acid position 127 to be replaced by a glycine (G). 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

0.19

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.77

M_CAP

Benign

0.014

MetaRNN

Benign

0.031

MetaSVM

Uncertain

-0.25

MutationAssessor

Uncertain

2.4

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.3

REVEL

Benign

0.26

Sift

Benign

0.33

Sift4G

Benign

0.22

Polyphen

1.0

Vest4

0.30

MVP

0.12

MPC

0.99

ClinPred

0.082

GERP RS

5.8

Varity_R

0.27

gMVP

0.21

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