Genetic Variant FAM89A:p.Val16Leu (chr1-231040166-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

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

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198552.3. 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
	FAM89A	NM_198552.3	MANE Select	c.46G>C	p.Val16Leu	missense	Exon 1 of 2	NP_940954.1	Q96GI7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM89A	ENST00000366654.5	TSL:1 MANE Select	c.46G>C	p.Val16Leu	missense	Exon 1 of 2	ENSP00000355614.4	Q96GI7
FAM89A	ENST00000951728.1		c.46G>C	p.Val16Leu	missense	Exon 1 of 3	ENSP00000621787.1
FAM89A	ENST00000951729.1		c.46G>C	p.Val16Leu	missense	Exon 1 of 3	ENSP00000621788.1

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

GnomAD2 exomes

AF:

0.0000919

AC:

AN:

10878

AF XY:

0.00

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 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

African (AFR)

AF:

0.0000476

AC:

AN:

21024

American (AMR)

AF:

0.000132

AC:

AN:

7580

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12506

East Asian (EAS)

AF:

0.00

AC:

AN:

21426

South Asian (SAS)

AF:

0.00

AC:

AN:

23434

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2696

European-Non Finnish (NFE)

AF:

0.000247

AC:

222

AN:

899690

Other (OTH)

AF:

0.0000745

AC:

AN:

40272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000182

AC:

AN:

148082

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

AN XY:

72246

show subpopulations

African (AFR)

AF:

0.0000734

AC:

AN:

40866

American (AMR)

AF:

0.0000669

AC:

AN:

14940

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3418

East Asian (EAS)

AF:

0.00

AC:

AN:

5050

South Asian (SAS)

AF:

0.00

AC:

AN:

4788

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9306

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000331

AC:

AN:

66464

Other (OTH)

AF:

0.000485

AC:

AN:

2060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000151

ExAC

AF:

0.000137

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

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

PhyloP100

1.7

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

PromoterAI

-0.071

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.078

gMVP

0.19

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over