chr11-67467566-G-A

Variant names:

• chr11-67467566-G-A
• NM_025124.4:c.264C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001078651.3(TMEM134):​c.240-3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM134 NM_001078651.3 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0660
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.157).
• BP6: Variant 11-67467566-G-A is Benign according to our data. Variant chr11-67467566-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3326785.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001078651.3. 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
	TMEM134	NM_025124.4	MANE Select	c.264C>T	p.Arg88Arg	synonymous	Exon 3 of 7	NP_079400.1	Q9H6X4-1
	TMEM134	NM_001078650.3		c.264C>T	p.Arg88Arg	synonymous	Exon 3 of 6	NP_001072118.1	Q9H6X4-2
	TMEM134	NM_001078651.3		c.240-3C>T		splice_region intron	N/A	NP_001072119.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM134	ENST00000308022.7	TSL:2 MANE Select	c.264C>T	p.Arg88Arg	synonymous	Exon 3 of 7	ENSP00000312615.2	Q9H6X4-1
	TMEM134	ENST00000393877.3	TSL:1	c.264C>T	p.Arg88Arg	synonymous	Exon 3 of 6	ENSP00000377455.3	Q9H6X4-2
	TMEM134	ENST00000501408.6	TSL:1	n.319C>T		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.6
DANN	Benign	0.81
PhyloP100		0.066
PromoterAI		0.0038	Neutral

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

hg19: chr11-67235037;