chr12-109744214-T-A

Position:

• chr12-109744214-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 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. 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: 4.37

Genes affected

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

FAM222A-AS1 (HGNC:):

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=0.2351084).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM222A	NM_032829.3	c.68T>A	p.Leu23Gln	missense_variant	2/3	ENST00000538780.2	NP_116218.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM222A	ENST00000538780.2	c.68T>A	p.Leu23Gln	missense_variant	2/3	1	NM_032829.3	ENSP00000443292.1
FAM222A	ENST00000358906.3	c.68T>A	p.Leu23Gln	missense_variant	2/3	5		ENSP00000351783.3
FAM222A-AS1	ENST00000541460.2	n.190-2049A>T		intron_variant		4
FAM222A-AS1	ENST00000541723.5	n.213-8393A>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

Aug 20, 2024

The c.68T>A (p.L23Q) alteration is located in exon 2 (coding exon 1) of the FAM222A gene. This alteration results from a T to A substitution at nucleotide position 68, causing the leucine (L) at amino acid position 23 to be replaced by a glutamine (Q). 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	0.096
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.094	T;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;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.19
Sift	Uncertain	0.0060	D;D
Sift4G	Benign	0.25	T;T
Polyphen		0.85	P;P
Vest4		0.55
MutPred		0.11		Gain of solvent accessibility (P = 0.0137);Gain of solvent accessibility (P = 0.0137);
MVP		0.14
MPC		0.26
ClinPred		0.86	D
GERP RS		3.9
Varity_R		0.31
gMVP		0.55

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: chr12-110182019;