Genetic Variant FAM222A:p.Thr134Pro (chr12-109768329-A-C) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 1P and 2B. PP2BP4_Moderate

The NM_032829.3(FAM222A):c.400A>C(p.Thr134Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000393 in 1,601,098 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts 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. T134A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000041 ( 1 hom. )

Consequence

FAM222A
NM_032829.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.42

Publications

0 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: Likely_benign. The variant received -1 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 1.1231 (below the threshold of 3.09). Trascript score misZ: -0.076601 (below the threshold of 3.09).

BP4

Computational evidence support a benign effect (MetaRNN=0.21673611).

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.400A>C	p.Thr134Pro	missense	Exon 3 of 3	NP_116218.2	Q5U5X8
FAM222A-AS1	NR_026661.2		n.191+4968T>G		intron	N/A
FAM222A-AS1	NR_026662.2		n.191+4968T>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM222A	ENST00000538780.2	TSL:1 MANE Select	c.400A>C	p.Thr134Pro	missense	Exon 3 of 3	ENSP00000443292.1	Q5U5X8
FAM222A	ENST00000358906.3	TSL:5	c.400A>C	p.Thr134Pro	missense	Exon 3 of 3	ENSP00000351783.3	Q5U5X8
FAM222A	ENST00000898959.1		c.400A>C	p.Thr134Pro	missense	Exon 2 of 2	ENSP00000569018.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000997

AC:

AN:

220600

AF XY:

0.000124

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000407

AC:

AN:

1448808

Hom.:

Cov.:

AF XY:

0.0000666

AC XY:

AN XY:

720220

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33256

American (AMR)

AF:

0.00

AC:

AN:

43478

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25892

East Asian (EAS)

AF:

0.00

AC:

AN:

39142

South Asian (SAS)

AF:

0.000599

AC:

AN:

85074

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.00000722

AC:

AN:

1107736

Other (OTH)

AF:

0.00

AC:

AN:

59922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152290

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41566

American (AMR)

AF:

0.00

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.000829

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000496

Hom.:

ExAC

AF:

0.0000912

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.83

M_CAP

Benign

0.082

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.3

PhyloP100

5.4

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.25

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.023

Polyphen

1.0

Vest4

0.70

MutPred

0.14

Gain of glycosylation at T134 (P = 0.027)

MVP

0.24

MPC

0.79

ClinPred

0.29

GERP RS

3.4

Varity_R

0.63

gMVP

0.67

Mutation Taster

=64/36

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