14-105529712-TGCCGCCGCCGCC-TGCCGCCGCCGCCGCCGCC

Variant names:

• chr14-105529723-C-CCGCCGC
• NM_025268.4:c.893_898dupCGCCGC

Variant summary

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

The NM_025268.4(TMEM121):​c.893_898dupCGCCGC​(p.Pro298_Pro299dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: TMEM121 NM_025268.4 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130
• Publications: 0 publications found

Genes affected

TMEM121 (HGNC:20511): (transmembrane protein 121) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025268.4. 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
	TMEM121	NM_025268.4	MANE Select	c.893_898dupCGCCGC	p.Pro298_Pro299dup	disruptive_inframe_insertion	Exon 2 of 2	NP_079544.1	Q9BTD3
	TMEM121	NM_001331238.2		c.893_898dupCGCCGC	p.Pro298_Pro299dup	disruptive_inframe_insertion	Exon 2 of 2	NP_001318167.1	Q9BTD3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM121	ENST00000392519.7	TSL:1 MANE Select	c.893_898dupCGCCGC	p.Pro298_Pro299dup	disruptive_inframe_insertion	Exon 2 of 2	ENSP00000376304.2	Q9BTD3
	TMEM121	ENST00000903730.1		c.893_898dupCGCCGC	p.Pro298_Pro299dup	disruptive_inframe_insertion	Exon 2 of 2	ENSP00000573789.1
	TMEM121	ENST00000903731.1		c.893_898dupCGCCGC	p.Pro298_Pro299dup	disruptive_inframe_insertion	Exon 2 of 2	ENSP00000573790.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.013

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr14-105996060;