Variant 12-109768407-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032829.3(FAM222A):c.478C>A(p.Pro160Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000076 in 1,446,456 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000076 ( 1 hom. )

Consequence

FAM222A
NM_032829.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0760

Variant links:

Genes affected

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

FAM222A links:

FAM222A-AS1 (HGNC:):

FAM222A-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.050275117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM222A	NM_032829.3 linkuse as main transcript	c.478C>A	p.Pro160Thr	missense_variant	3/3	ENST00000538780.2	NP_116218.2	Q5U5X8A0A024RBN3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FAM222A	ENST00000538780.2 linkuse as main transcript	c.478C>A	p.Pro160Thr	missense_variant	3/3	1	NM_032829.3	ENSP00000443292.1	Q5U5X8
FAM222A	ENST00000358906.3 linkuse as main transcript	c.478C>A	p.Pro160Thr	missense_variant	3/3	5		ENSP00000351783.3	Q5U5X8
FAM222A-AS1	ENST00000541460.2 linkuse as main transcript	n.189+4890G>T		intron_variant		4
FAM222A-AS1	ENST00000541723.5 linkuse as main transcript	n.212+4890G>T		intron_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000270

AC:

AN:

222096

Hom.:

AF XY:

0.0000404

AC XY:

AN XY:

123676

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 SAS exome

AF:

0.000201

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000760

AC:

AN:

1446456

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

719828

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000335

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2024

The c.478C>A (p.P160T) alteration is located in exon 3 (coding exon 2) of the FAM222A gene. This alteration results from a C to A substitution at nucleotide position 478, causing the proline (P) at amino acid position 160 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.59

CADD

Benign

3.3

DANN

Benign

0.96

DEOGEN2

Benign

0.098

T;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.56

.;T

M_CAP

Benign

0.044

MetaRNN

Benign

0.050

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.040

Sift

Benign

0.13

T;T

Sift4G

Benign

0.083

T;T

Polyphen

0.032

B;B

Vest4

0.21

MutPred

0.21

Gain of phosphorylation at P160 (P = 0.0341);Gain of phosphorylation at P160 (P = 0.0341);

MVP

0.030

MPC

0.21

ClinPred

0.047

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.090

gMVP

0.26

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