12-109744202-C-T

Variant names:

• chr12-109744202-C-T
• rs146405681
• NM_032829.3:c.56C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032829.3(FAM222A):​c.56C>T​(p.Pro19Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,613,186 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: FAM222A NM_032829.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.90

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19149548).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM222A	NM_032829.3	c.56C>T	p.Pro19Leu	missense_variant	Exon 2 of 3	ENST00000538780.2	NP_116218.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM222A	ENST00000538780.2	c.56C>T	p.Pro19Leu	missense_variant	Exon 2 of 3	1	NM_032829.3	ENSP00000443292.1
FAM222A	ENST00000358906.3	c.56C>T	p.Pro19Leu	missense_variant	Exon 2 of 3	5		ENSP00000351783.3
FAM222A-AS1	ENST00000541460.2	n.190-2037G>A		intron_variant	Intron 1 of 3	4
FAM222A-AS1	ENST00000541723.5	n.213-8381G>A		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152220 Hom.: 0 Cov.: 33

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1460966 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 726866

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152220 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74362

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000205 Hom.: 0

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.082	T;T
Eigen	Benign	0.052
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	.;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-4.0	D;D
REVEL	Benign	0.13
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.023	D;D
Polyphen		0.0020	B;B
Vest4		0.65
MutPred		0.19		Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);
MVP		0.14
MPC		0.24
ClinPred		0.97	D
GERP RS		5.1
Varity_R		0.18
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs146405681; hg19: chr12-110182007;