dbSNP rs1338068289: FAM90A1:p.Ala337Ser (chr12-8222208-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_018088.3(FAM90A1):c.1009G>T(p.Ala337Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,666 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A337T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FAM90A1
NM_018088.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.737

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:

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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=0.057732165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM90A1	NM_018088.3 link	c.1009G>T	p.Ala337Ser	missense_variant	Exon 7 of 7	ENST00000538603.6	NP_060558.3	Q86YD7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM90A1	ENST00000538603.6 link	c.1009G>T	p.Ala337Ser	missense_variant	Exon 7 of 7	1	NM_018088.3	ENSP00000445418.1		Q86YD7
FAM90A1	ENST00000307435.10 link	c.1009G>T	p.Ala337Ser	missense_variant	Exon 6 of 6	2		ENSP00000307798.6		Q86YD7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459666

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726118

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.23

DANN

Benign

0.38

DEOGEN2

Benign

0.0013

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.46

.;T

M_CAP

Benign

0.0010

MetaRNN

Benign

0.058

T;T

MetaSVM

Benign

-0.96

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.0080

Sift

Benign

0.091

T;T

Sift4G

Benign

0.64

T;T

Polyphen

0.17

B;B

Vest4

0.084

MutPred

0.18

Gain of glycosylation at A337 (P = 0.0122);Gain of glycosylation at A337 (P = 0.0122);

MVP

0.12

MPC

0.36

ClinPred

0.10

GERP RS

-1.3

Varity_R

0.045

gMVP

0.057

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over