Genetic Variant FAM222A:p.Ser33Ser (chr12-109768028-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_032829.3(FAM222A):c.99C>T(p.Ser33Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00343 in 1,613,126 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0036 ( 15 hom. )

Consequence

FAM222A
NM_032829.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.472

Publications

1 publications found

Variant links:

Genes affected

FAM222A (HGNC:25915): (family with sequence similarity 222 member A)

FAM222A links:

FAM222A-AS1 (HGNC:28223): (FAM222A antisense RNA 1)

FAM222A-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 12-109768028-C-T is Benign according to our data. Variant chr12-109768028-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3770954.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.472 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032829.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM222A	NM_032829.3	MANE Select	c.99C>T	p.Ser33Ser	synonymous	Exon 3 of 3	NP_116218.2	Q5U5X8
FAM222A-AS1	NR_026661.2		n.191+5269G>A		intron	N/A
FAM222A-AS1	NR_026662.2		n.191+5269G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM222A	ENST00000538780.2	TSL:1 MANE Select	c.99C>T	p.Ser33Ser	synonymous	Exon 3 of 3	ENSP00000443292.1	Q5U5X8
FAM222A	ENST00000358906.3	TSL:5	c.99C>T	p.Ser33Ser	synonymous	Exon 3 of 3	ENSP00000351783.3	Q5U5X8
FAM222A	ENST00000898959.1		c.99C>T	p.Ser33Ser	synonymous	Exon 2 of 2	ENSP00000569018.1

Frequencies

GnomAD3 genomes

AF:

0.00213

AC:

324

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00375

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.00189

AC:

471

AN:

249790

AF XY:

0.00187

show subpopulations

Gnomad AFR exome

AF:

0.000990

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000703

Gnomad NFE exome

AF:

0.00318

Gnomad OTH exome

AF:

0.00197

GnomAD4 exome

AF:

0.00357

AC:

5211

AN:

1460830

Hom.:

Cov.:

AF XY:

0.00348

AC XY:

2526

AN XY:

726708

show subpopulations

African (AFR)

AF:

0.000747

AC:

AN:

33480

American (AMR)

AF:

0.00134

AC:

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26096

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000916

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.000683

AC:

AN:

52742

Middle Eastern (MID)

AF:

0.000694

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00432

AC:

4803

AN:

1111760

Other (OTH)

AF:

0.00333

AC:

201

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

311

622

932

1243

1554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

194

388

582

776

970

<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:

0.00213

AC:

324

AN:

152296

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

134

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000842

AC:

AN:

41550

American (AMR)

AF:

0.000915

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00141

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00375

AC:

255

AN:

68012

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00264

Hom.:

Bravo

AF:

0.00223

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00354

EpiControl

AF:

0.00338

ClinVar

ClinVar submissions

Significance:Likely 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

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

0.47

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over