rs1353147768

Variant names:

• chr11-67469020-T-A
• rs1353147768
• NM_025124.4:c.173A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-67469020-T-A
• chr11-67469020-T-C
• chr11-67469020-T-G

Variant summary

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

The NM_025124.4(TMEM134):​c.173A>T​(p.Gln58Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000743 in 1,346,608 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: TMEM134 NM_025124.4 missense, splice_region
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.40

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM134	NM_025124.4	c.173A>T	p.Gln58Leu	missense_variant, splice_region_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.173A>T	p.Gln58Leu	missense_variant, splice_region_variant	Exon 1 of 7	2	NM_025124.4	ENSP00000312615.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.43e-7 AC: 1 AN: 1346608 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 664564

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000311

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: 0.00

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	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	34
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.58	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.7	N;D
REVEL	Benign	0.27
Sift	Uncertain	0.0040	D;D
Sift4G	Benign	0.078	T;T
Polyphen		0.97	D;P
Vest4		0.52
MutPred		0.51		Loss of solvent accessibility (P = 0.0635);Loss of solvent accessibility (P = 0.0635);
MVP		0.25
MPC		0.35
ClinPred		0.92	D
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.51
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.99
SpliceAI score (max)		0.19		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: rs1353147768; hg19: chr11-67236491;