NM_025124.4:c.7G>A

Variant names:

• chr11-67469186-C-T
• rs536544835
• NM_025124.4:c.7G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025124.4(TMEM134):​c.7G>A​(p.Ala3Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000253 in 1,186,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict 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)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: TMEM134 NM_025124.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620

Genes affected

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

AIP (HGNC:358): (aryl hydrocarbon receptor interacting protein) The protein encoded by this gene is a receptor for aryl hydrocarbons and a ligand-activated transcription factor. The encoded protein is found in the cytoplasm as part of a multiprotein complex, but upon binding of ligand is transported to the nucleus. This protein can regulate the expression of many xenobiotic metabolizing enzymes. Also, the encoded protein can bind specifically to and inhibit the activity of hepatitis B virus. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]

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=0.073331624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM134	NM_025124.4	c.7G>A	p.Ala3Thr	missense_variant	Exon 1 of 7	ENST00000308022.7	NP_079400.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM134	ENST00000308022.7	c.7G>A	p.Ala3Thr	missense_variant	Exon 1 of 7	2	NM_025124.4	ENSP00000312615.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000253 AC: 3 AN: 1186286 Hom.: 0 Cov.: 31 AF XY: 0.00000349 AC XY: 2 AN XY: 573652

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000310

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0072	T;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.70	T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.073	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.52	N;N
REVEL	Benign	0.038
Sift	Uncertain	0.011	D;D
Sift4G	Uncertain	0.032	D;D
Polyphen		0.51	P;B
Vest4		0.15
MutPred		0.32		Gain of glycosylation at A3 (P = 0.002);Gain of glycosylation at A3 (P = 0.002);
MVP		0.048
MPC		0.070
ClinPred		0.20	T
GERP RS		-0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.14
gMVP		0.14

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

LitVar

Other links and lift over

dbSNP: rs536544835; hg19: chr11-67236657;