chr12-109744214-T-A

Variant names:

• chr12-109744214-T-A
• NM_032829.3:c.68T>A
• FAM222A p.Leu23Gln

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_032829.3(FAM222A):​c.68T>A​(p.Leu23Gln) 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. 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: 4.37
• Publications: 0 publications found

Genes affected

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

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 1.1231 (below the threshold of 3.09). Trascript score misZ: -0.076601 (below the threshold of 3.09).
• BP4: Computational evidence support a benign effect (MetaRNN=0.2351084).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032829.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM222A	NM_032829.3	MANE Select	c.68T>A	p.Leu23Gln	missense	Exon 2 of 3	NP_116218.2	Q5U5X8
	FAM222A-AS1	NR_026661.2		n.192-2049A>T		intron	N/A
	FAM222A-AS1	NR_026662.2		n.192-8393A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM222A	ENST00000538780.2	TSL:1 MANE Select	c.68T>A	p.Leu23Gln	missense	Exon 2 of 3	ENSP00000443292.1	Q5U5X8
	FAM222A	ENST00000358906.3	TSL:5	c.68T>A	p.Leu23Gln	missense	Exon 2 of 3	ENSP00000351783.3	Q5U5X8
	FAM222A	ENST00000898959.1		c.68T>A	p.Leu23Gln	missense	Exon 1 of 2	ENSP00000569018.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.094	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.4
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.19
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.25	T
Varity_R		0.31
gMVP		0.55
Mutation Taster		=73/27	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-110182019;