Variant chr12-109768012-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032829.3(FAM222A):c.83G>A(p.Cys28Tyr) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FAM222A
NM_032829.3 missense, splice_region

Scores

Splicing: ADA: 0.06505

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.17

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31604117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM222A	NM_032829.3 linkuse as main transcript	c.83G>A	p.Cys28Tyr	missense_variant, splice_region_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.83G>A	p.Cys28Tyr	missense_variant, splice_region_variant	3/3	1	NM_032829.3	ENSP00000443292.1	Q5U5X8
FAM222A	ENST00000358906.3 linkuse as main transcript	c.83G>A	p.Cys28Tyr	missense_variant, splice_region_variant	3/3	5		ENSP00000351783.3	Q5U5X8
FAM222A-AS1	ENST00000541460.2 linkuse as main transcript	n.189+5285C>T		intron_variant		4
FAM222A-AS1	ENST00000541723.5 linkuse as main transcript	n.212+5285C>T		intron_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458912

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725526

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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 06, 2022

The c.83G>A (p.C28Y) alteration is located in exon 3 (coding exon 2) of the FAM222A gene. This alteration results from a G to A substitution at nucleotide position 83, causing the cysteine (C) at amino acid position 28 to be replaced by a tyrosine (Y). 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

0.32

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Benign

0.90

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

0.0089

Eigen_PC

Benign

0.065

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.70

.;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.32

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.22

Sift

Benign

0.12

T;T

Sift4G

Benign

0.84

T;T

Polyphen

0.24

B;B

Vest4

0.61

MutPred

0.35

Loss of methylation at K27 (P = 0.0331);Loss of methylation at K27 (P = 0.0331);

MVP

0.085

MPC

0.34

ClinPred

0.68

GERP RS

3.2

Varity_R

0.22

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.065

dbscSNV1_RF

Benign

0.31

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