chr11-67467558-T-C

Variant names:

• chr11-67467558-T-C
• rs1865347941
• NM_025124.4:c.272A>G

Variant summary

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

The NM_025124.4(TMEM134):​c.272A>G​(p.Gln91Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. Q91P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TMEM134 NM_025124.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1649732).

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.272A>G	p.Gln91Arg	missense	Exon 3 of 7	NP_079400.1	Q9H6X4-1
	TMEM134	NM_001078651.3		c.245A>G	p.Gln82Arg	missense	Exon 3 of 7	NP_001072119.1
	TMEM134	NM_001078650.3		c.272A>G	p.Gln91Arg	missense	Exon 3 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.272A>G	p.Gln91Arg	missense	Exon 3 of 7	ENSP00000312615.2	Q9H6X4-1
	TMEM134	ENST00000393877.3	TSL:1	c.272A>G	p.Gln91Arg	missense	Exon 3 of 6	ENSP00000377455.3	Q9H6X4-2
	TMEM134	ENST00000501408.6	TSL:1	n.327A>G		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152124 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: 0.00000137 AC: 2 AN: 1461808 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727200

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152124 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74316

African (AFR) AF: 0.00 AC: 0 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.028	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.0
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.090
Sift	Benign	0.35	T
Sift4G	Benign	0.33	T
Polyphen		0.20	B
Vest4		0.41
MutPred		0.58		Gain of MoRF binding (P = 0.0477)
MVP		0.17
MPC		0.25
ClinPred		0.72	D
GERP RS		4.4
PromoterAI		-0.031	Neutral
Varity_R		0.12
gMVP		0.40
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1865347941; hg19: chr11-67235029;