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

Variant summary

Our verdict is Benign. The variant received -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

Publications

18 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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.1031_1032insCGT	p.Thr344_Ser345insVal	disruptive_inframe_insertion	Exon 7 of 7	NP_060558.3	Q86YD7
	FAM90A1	NM_001319982.2		c.1031_1032insCGT	p.Thr344_Ser345insVal	disruptive_inframe_insertion	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.1031_1032insCGT	p.Thr344_Ser345insVal	disruptive_inframe_insertion	Exon 7 of 7	ENSP00000445418.1	Q86YD7
FAM90A1	ENST00000307435.10	TSL:2	c.1031_1032insCGT	p.Thr344_Ser345insVal	disruptive_inframe_insertion	Exon 6 of 6	ENSP00000307798.6	Q86YD7
FAM90A1	ENST00000890758.1		c.1031_1032insCGT	p.Thr344_Ser345insVal	disruptive_inframe_insertion	Exon 7 of 7	ENSP00000560817.1

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

African (AFR)

AF:

0.151

AC:

5052

AN:

33416

American (AMR)

AF:

0.437

AC:

19499

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.631

AC:

16498

AN:

26130

East Asian (EAS)

AF:

0.525

AC:

20827

AN:

39664

South Asian (SAS)

AF:

0.466

AC:

40142

AN:

86118

European-Finnish (FIN)

AF:

0.665

AC:

35371

AN:

53176

Middle Eastern (MID)

AF:

0.594

AC:

2592

AN:

4360

European-Non Finnish (NFE)

AF:

0.728

AC:

808813

AN:

1111524

Other (OTH)

AF:

0.638

AC:

38427

AN:

60206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.537

Heterozygous variant carriers

14493

28986

43478

57971

72464

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20152

40304

60456

80608

100760

<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:

0.526

AC:

79903

AN:

151930

Hom.:

23703

Cov.:

AF XY:

0.522

AC XY:

38747

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.171

AC:

7096

AN:

41458

American (AMR)

AF:

0.501

AC:

7649

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.618

AC:

2140

AN:

3464

East Asian (EAS)

AF:

0.533

AC:

2745

AN:

5146

South Asian (SAS)

AF:

0.463

AC:

2224

AN:

4802

European-Finnish (FIN)

AF:

0.656

AC:

6912

AN:

10536

Middle Eastern (MID)

AF:

0.629

AC:

185

AN:

294

European-Non Finnish (NFE)

AF:

0.723

AC:

49124

AN:

67934

Other (OTH)

AF:

0.566

AC:

1195

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

1182

2365

3547

4730

5912

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

690

1380

2070

2760

3450

<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:

0.566

Hom.:

3101

Asia WGS

AF:

0.457

AC:

1593

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-3.6

Mutation Taster

=89/11

polymorphism (auto)

(source)

Splicing

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