Genetic Variant FAM90A1:p.Leu408Leu (chr12-8221993-C-G) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_018088.3(FAM90A1):c.1224G>C(p.Leu408Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000293 in 1,597,348 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00045 ( 1 hom., cov: 34)

Exomes 𝑓: 0.00028 ( 2 hom. )

Consequence

FAM90A1
NM_018088.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0650

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 Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.05).

BP6

Variant 12-8221993-C-G is Benign according to our data. Variant chr12-8221993-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2642686.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.065 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM90A1	NM_018088.3 link	c.1224G>C	p.Leu408Leu	synonymous_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.1224G>C	p.Leu408Leu	synonymous_variant	Exon 7 of 7	1	NM_018088.3	ENSP00000445418.1		Q86YD7
FAM90A1	ENST00000307435.10 link	c.1224G>C	p.Leu408Leu	synonymous_variant	Exon 6 of 6	2		ENSP00000307798.6		Q86YD7

Frequencies

GnomAD3 genomes

AF:

0.000453

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00501

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000428

AC:

101

AN:

235740

Hom.:

AF XY:

0.000479

AC XY:

AN XY:

129562

show subpopulations

Gnomad AFR exome

AF:

0.000140

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.000605

Gnomad EAS exome

AF:

0.00188

Gnomad SAS exome

AF:

0.000851

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000237

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000277

AC:

400

AN:

1445022

Hom.:

Cov.:

AF XY:

0.000286

AC XY:

206

AN XY:

719280

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.000459

Gnomad4 EAS exome

AF:

0.00106

Gnomad4 SAS exome

AF:

0.000650

Gnomad4 FIN exome

AF:

0.0000757

Gnomad4 NFE exome

AF:

0.000216

Gnomad4 OTH exome

AF:

0.000516

GnomAD4 genome

AF:

0.000446

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00483

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000400

Hom.:

Bravo

AF:

0.000400

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FAM90A1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.35

DANN

Benign

0.44

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