12-109768185-G-A

Variant names:

• chr12-109768185-G-A
• NM_032829.3:c.256G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032829.3(FAM222A):​c.256G>A​(p.Gly86Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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)
• Consequence: FAM222A NM_032829.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.10

Genes affected

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

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

ACMG classification

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=0.38350832).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM222A	NM_032829.3	c.256G>A	p.Gly86Ser	missense_variant	Exon 3 of 3	ENST00000538780.2	NP_116218.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM222A	ENST00000538780.2	c.256G>A	p.Gly86Ser	missense_variant	Exon 3 of 3	1	NM_032829.3	ENSP00000443292.1
FAM222A	ENST00000358906.3	c.256G>A	p.Gly86Ser	missense_variant	Exon 3 of 3	5		ENSP00000351783.3
FAM222A-AS1	ENST00000541460.2	n.189+5112C>T		intron_variant	Intron 1 of 3	4
FAM222A-AS1	ENST00000541723.5	n.212+5112C>T		intron_variant	Intron 1 of 2	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

Jan 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.256G>A (p.G86S) 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 256, causing the glycine (G) at amino acid position 86 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	Benign	0.091
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	T;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	.;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.38	T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Benign	0.22
Sift	Uncertain	0.017	D;D
Sift4G	Benign	0.12	T;T
Polyphen		0.69	P;P
Vest4		0.57
MutPred		0.21		Gain of glycosylation at G86 (P = 0.0103);Gain of glycosylation at G86 (P = 0.0103);
MVP		0.21
MPC		0.69
ClinPred		0.98	D
GERP RS		3.4
Varity_R		0.49
gMVP		0.49

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: chr12-110205990;