14-105529712-TGCCGCCGCCGCC-TGCCGCCGCCGCCGCCGCC

Variant names:

• chr14-105529712-T-TGCCGCC
• rs10569304
• NM_025268.4:c.893_898dupCGCCGC

Variant summary

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

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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000051 (0 hom.)
• Consequence: TMEM121 NM_025268.4 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.501
• 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 0 ACMG points.

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 AF: 0.00000659 AC: 1 AN: 151668 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000509 AC: 7 AN: 1375900 Hom.: 0 Cov.: 12 AF XY: 0.00000884 AC XY: 6 AN XY: 678950

African (AFR) AF: 0.00 AC: 0 AN: 30462

American (AMR) AF: 0.00 AC: 0 AN: 34708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24678

East Asian (EAS) AF: 0.00 AC: 0 AN: 35174

South Asian (SAS) AF: 0.00 AC: 0 AN: 78376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34258

Middle Eastern (MID) AF: 0.000372 AC: 2 AN: 5378

European-Non Finnish (NFE) AF: 0.00000465 AC: 5 AN: 1075456

Other (OTH) AF: 0.00 AC: 0 AN: 57410

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151776 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 74188

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41372

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5118

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10540

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67860

Other (OTH) AF: 0.00 AC: 0 AN: 2110

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.50
Mutation Taster		=85/15	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs10569304; hg19: chr14-105996049;