11-67464809-G-C

Variant names:

• chr11-67464809-G-C
• rs1268477832
• NM_025124.4:c.499C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_025124.4(TMEM134):​c.499C>G​(p.Pro167Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. P167S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM134 NM_025124.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.39
• Publications: 0 publications found

Genes affected

TMEM134 (HGNC:26142): (transmembrane protein 134) Located in cytosol and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.83

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025124.4. 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
	TMEM134	NM_025124.4	MANE Select	c.499C>G	p.Pro167Ala	missense	Exon 6 of 7	NP_079400.1	Q9H6X4-1
	TMEM134	NM_001078651.3		c.472C>G	p.Pro158Ala	missense	Exon 6 of 7	NP_001072119.1
	TMEM134	NM_001078650.3		c.454C>G	p.Pro152Ala	missense	Exon 5 of 6	NP_001072118.1	Q9H6X4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM134	ENST00000308022.7	TSL:2 MANE Select	c.499C>G	p.Pro167Ala	missense	Exon 6 of 7	ENSP00000312615.2	Q9H6X4-1
	TMEM134	ENST00000393877.3	TSL:1	c.454C>G	p.Pro152Ala	missense	Exon 5 of 6	ENSP00000377455.3	Q9H6X4-2
	TMEM134	ENST00000545682.5	TSL:1	n.*87C>G		non_coding_transcript_exon	Exon 6 of 7	ENSP00000438439.1	Q9H6X4-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 235242 AF XY: 0.00

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.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.4
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-7.5	D
REVEL	Uncertain	0.44
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.63
MutPred		0.71		Gain of catalytic residue at P167 (P = 0.011)
MVP		0.25
MPC		0.42
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.86
gMVP		0.94
Mutation Taster		=67/33	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: rs1268477832; hg19: chr11-67232280;