Genetic Variant NM_198552.3:c.44C>T (chr1-231040168-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198552.3(FAM89A):c.44C>T(p.Ala15Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000674 in 1,186,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000038 ( 0 hom. )

Consequence

FAM89A
NM_198552.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.418

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06649825).

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.44C>T	p.Ala15Val	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.44C>T	p.Ala15Val	missense	Exon 1 of 2	ENSP00000355614.4	Q96GI7
FAM89A	ENST00000951728.1		c.44C>T	p.Ala15Val	missense	Exon 1 of 3	ENSP00000621787.1
FAM89A	ENST00000951729.1		c.44C>T	p.Ala15Val	missense	Exon 1 of 3	ENSP00000621788.1

Frequencies

GnomAD3 genomes

AF:

0.0000271

AC:

AN:

147490

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000986

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000385

AC:

AN:

1039366

Hom.:

Cov.:

AF XY:

0.00000202

AC XY:

AN XY:

494674

show subpopulations

African (AFR)

AF:

0.0000961

AC:

AN:

20804

American (AMR)

AF:

0.00

AC:

AN:

7154

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12146

East Asian (EAS)

AF:

0.00

AC:

AN:

20956

South Asian (SAS)

AF:

0.00

AC:

AN:

22364

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19078

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2670

European-Non Finnish (NFE)

AF:

0.00000112

AC:

AN:

894326

Other (OTH)

AF:

0.0000251

AC:

AN:

39868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

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:

0.0000271

AC:

AN:

147490

Hom.:

Cov.:

AF XY:

0.0000418

AC XY:

AN XY:

71856

show subpopulations

African (AFR)

AF:

0.0000986

AC:

AN:

40560

American (AMR)

AF:

0.00

AC:

AN:

14892

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3412

East Asian (EAS)

AF:

0.00

AC:

AN:

5020

South Asian (SAS)

AF:

0.00

AC:

AN:

4760

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9262

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66350

Other (OTH)

AF:

0.00

AC:

AN:

2032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

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:

0.00000756

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

0.14

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.010

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.41

M_CAP

Benign

0.0019

MetaRNN

Benign

0.066

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

0.42

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.78

REVEL

Benign

0.041

Sift

Benign

0.053

Sift4G

Benign

0.14

Polyphen

0.13

Vest4

0.12

MutPred

0.24

Gain of sheet (P = 0.0477)

MVP

0.014

MPC

0.29

ClinPred

0.096

GERP RS

-0.47

PromoterAI

0.013

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.039

gMVP

0.20

Mutation Taster

=96/4

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

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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