Genetic Variant FAM90A1:p.Thr344_Ser345insVal (chr12-8222185-C-CACG) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PM4_SupportingBP6_ModerateBA1

The NM_018088.3(FAM90A1):c.1031_1032insCGT(p.Thr344_Ser345insVal) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.53 ( 23703 hom., cov: 0)

Exomes 𝑓: 0.68 ( 326290 hom. )

Failed GnomAD Quality Control

Consequence

FAM90A1
NM_018088.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.63

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_018088.3. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 12-8222185-C-CACG is Benign according to our data. Variant chr12-8222185-C-CACG is described in ClinVar as [Benign]. Clinvar id is 768513.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM90A1	NM_018088.3 link	c.1031_1032insCGT	p.Thr344_Ser345insVal	disruptive_inframe_insertion	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.1031_1032insCGT	p.Thr344_Ser345insVal	disruptive_inframe_insertion	Exon 7 of 7	1	NM_018088.3	ENSP00000445418.1		Q86YD7
FAM90A1	ENST00000307435.10 link	c.1031_1032insCGT	p.Thr344_Ser345insVal	disruptive_inframe_insertion	Exon 6 of 6	2		ENSP00000307798.6		Q86YD7

Frequencies

GnomAD3 genomes

AF:

0.526

AC:

79918

AN:

151812

Hom.:

23709

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.697

Gnomad AMR

AF:

0.501

Gnomad ASJ

AF:

0.618

Gnomad EAS

AF:

0.534

Gnomad SAS

AF:

0.462

Gnomad FIN

AF:

0.656

Gnomad MID

AF:

0.623

Gnomad NFE

AF:

0.723

Gnomad OTH

AF:

0.569

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.677

AC:

987221

AN:

1459264

Hom.:

326290

Cov.:

AF XY:

0.672

AC XY:

488091

AN XY:

725930

show subpopulations

Gnomad4 AFR exome

AF:

0.151

Gnomad4 AMR exome

AF:

0.437

Gnomad4 ASJ exome

AF:

0.631

Gnomad4 EAS exome

AF:

0.525

Gnomad4 SAS exome

AF:

0.466

Gnomad4 FIN exome

AF:

0.665

Gnomad4 NFE exome

AF:

0.728

Gnomad4 OTH exome

AF:

0.638

GnomAD4 genome

AF:

0.526

AC:

79903

AN:

151930

Hom.:

23703

Cov.:

AF XY:

0.522

AC XY:

38747

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.171

Gnomad4 AMR

AF:

0.501

Gnomad4 ASJ

AF:

0.618

Gnomad4 EAS

AF:

0.533

Gnomad4 SAS

AF:

0.463

Gnomad4 FIN

AF:

0.656

Gnomad4 NFE

AF:

0.723

Gnomad4 OTH

AF:

0.566

Alfa

AF:

0.566

Hom.:

3101

Asia WGS

AF:

0.457

AC:

1593

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 09, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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