chr4-1717567-T-G

Variant names:

• chr4-1717567-T-G
• rs2236786
• NM_001127266.2:c.789A>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001127266.2(TMEM129):​c.789A>C​(p.Thr263Thr) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: TMEM129 NM_001127266.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.22
• Publications: 16 publications found

Genes affected

TMEM129 (HGNC:25137): (transmembrane protein 129, E3 ubiquitin ligase) Enables ubiquitin protein ligase activity. Involved in protein polyubiquitination; retrograde protein transport, ER to cytosol; and ubiquitin-dependent ERAD pathway. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

TACC3 (HGNC:11524): (transforming acidic coiled-coil containing protein 3) This gene encodes a member of the transforming acidic colied-coil protein family. The encoded protein is a motor spindle protein that may play a role in stabilization of the mitotic spindle. This protein may also play a role in growth a differentiation of certain cancer cells. [provided by RefSeq, Nov 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=-4.22 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127266.2. 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
	TMEM129	NM_001127266.2	MANE Select	c.789A>C	p.Thr263Thr	synonymous	Exon 3 of 4	NP_001120738.1
	TMEM129	NM_138385.4		c.681-139A>C		intron	N/A	NP_612394.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM129	ENST00000382936.8	TSL:1 MANE Select	c.789A>C	p.Thr263Thr	synonymous	Exon 3 of 4	ENSP00000372394.3
	TMEM129	ENST00000303277.6	TSL:1	c.681-139A>C		intron	N/A	ENSP00000305243.2
	TMEM129	ENST00000460722.1	TSL:1	n.*136A>C		non_coding_transcript_exon	Exon 2 of 3	ENSP00000417412.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 2925

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.65
PhyloP100		-4.2

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: rs2236786; hg19: chr4-1719294;