Genetic Variant NM_018088.3:c.1143C>A (chr12-8222074-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018088.3(FAM90A1):c.1143C>A(p.His381Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FAM90A1
NM_018088.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

Publications

0 publications found

Variant links:

Genes affected

FAM90A1 (HGNC:25526): (family with sequence similarity 90 member A1) FAM90A1 belongs to subfamily I of the primate-specific FAM90A gene family, which originated from multiple duplications and rearrangements (Bosch et al., 2007 [PubMed 17684299]).[supplied by OMIM, Oct 2009]

FAM90A1 links:

FAM66C (HGNC:21644): (family with sequence similarity 66 member C)

FAM66C links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09790039).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018088.3. 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
	FAM90A1	NM_018088.3	MANE Select	c.1143C>A	p.His381Gln	missense	Exon 7 of 7	NP_060558.3	Q86YD7
	FAM90A1	NM_001319982.2		c.1143C>A	p.His381Gln	missense	Exon 6 of 6	NP_001306911.1	Q86YD7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM90A1	ENST00000538603.6	TSL:1 MANE Select	c.1143C>A	p.His381Gln	missense	Exon 7 of 7	ENSP00000445418.1	Q86YD7
FAM90A1	ENST00000307435.10	TSL:2	c.1143C>A	p.His381Gln	missense	Exon 6 of 6	ENSP00000307798.6	Q86YD7
FAM90A1	ENST00000890758.1		c.1143C>A	p.His381Gln	missense	Exon 7 of 7	ENSP00000560817.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.87e-7

AC:

AN:

1455756

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724376

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33414

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86170

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49176

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4274

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111964

Other (OTH)

AF:

0.00

AC:

AN:

60198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

0.20

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

6.2

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0017

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0032

LIST_S2

Benign

0.36

M_CAP

Benign

0.00083

MetaRNN

Benign

0.098

MetaSVM

Benign

-0.98

PhyloP100

1.0

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.4

REVEL

Benign

0.041

Sift

Benign

0.40

Sift4G

Benign

0.55

Polyphen

0.55

Vest4

0.21

MutPred

0.27

Loss of catalytic residue at H381 (P = 0.1384)

MVP

0.085

MPC

0.50

ClinPred

0.17

GERP RS

-2.0

Varity_R

0.065

gMVP

0.040

Mutation Taster

=100/0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over