rs774049520

Variant names:

• chr1-27333980-C-G
• rs774049520
• NM_032125.3:c.334C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-27333980-C-G
• chr1-27333980-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032125.3(TMEM222):​c.334C>G​(p.Gln112Glu) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q112R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM222 NM_032125.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.56
• Publications: 0 publications found

Genes affected

TMEM222 (HGNC:25363): (transmembrane protein 222) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM222 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with motor and speech delay and behavioral abnormalities

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, LiferaOmics, Labcorp Genetics (formerly Invitae), G2P

ENSG00000304055 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17484745).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032125.3. 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
	TMEM222	NM_032125.3	MANE Select	c.334C>G	p.Gln112Glu	missense	Exon 4 of 6	NP_115501.2	Q9H0R3-1
	TMEM222	NR_037576.2		n.440C>G		non_coding_transcript_exon	Exon 5 of 7
	TMEM222	NR_037577.2		n.287C>G		non_coding_transcript_exon	Exon 4 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM222	ENST00000374076.9	TSL:1 MANE Select	c.334C>G	p.Gln112Glu	missense	Exon 4 of 6	ENSP00000363189.4	Q9H0R3-1
	TMEM222	ENST00000611517.4	TSL:1	c.334C>G	p.Gln112Glu	missense	Exon 4 of 6	ENSP00000483276.1	Q9H0R3-1
	TMEM222	ENST00000608611.5	TSL:1	c.235C>G	p.Gln79Glu	missense	Exon 4 of 6	ENSP00000476439.1	Q8TDQ4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250732 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.023	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.6
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.034
Sift	Benign	0.43	T
Sift4G	Benign	0.29	T
Polyphen		0.0090	B
Vest4		0.30
MutPred		0.42		Gain of ubiquitination at K107 (P = 0.0619)
MVP		0.11
MPC		0.37
ClinPred		0.25	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.090
gMVP		0.52
Mutation Taster		=81/19	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

Other links and lift over

dbSNP: rs774049520; hg19: chr1-27660471;