chr12-109768191-C-A

Position:

• chr12-109768191-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032829.3(FAM222A):​c.262C>A​(p.Arg88Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM222A NM_032829.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.51

Genes affected

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

FAM222A-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM222A	NM_032829.3	c.262C>A	p.Arg88Ser	missense_variant	3/3	ENST00000538780.2	NP_116218.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM222A	ENST00000538780.2	c.262C>A	p.Arg88Ser	missense_variant	3/3	1	NM_032829.3	ENSP00000443292.1
FAM222A	ENST00000358906.3	c.262C>A	p.Arg88Ser	missense_variant	3/3	5		ENSP00000351783.3
FAM222A-AS1	ENST00000541460.2	n.189+5106G>T		intron_variant		4
FAM222A-AS1	ENST00000541723.5	n.212+5106G>T		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 14, 2021

The c.262C>A (p.R88S) 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 262, causing the arginine (R) at amino acid position 88 to be replaced by a serine (S). 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	Pathogenic	0.78
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	.;D
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-0.40	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-5.2	D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.034	D;D
Polyphen		1.0	D;D
Vest4		0.88
MutPred		0.30		Gain of glycosylation at R88 (P = 0.0095);Gain of glycosylation at R88 (P = 0.0095);
MVP		0.30
MPC		0.73
ClinPred		0.99	D
GERP RS		3.4
Varity_R		0.88
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-110205996;