chr14-56585009-ATC-A

Variant names:

• chr14-56585009-ATC-A
• NM_017799.4:c.170_171delTC

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_017799.4(TMEM260):​c.170_171delTC​(p.Ile57AsnfsTer5) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM260 NM_017799.4 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 7.64
• Publications: 0 publications found

Genes affected

TMEM260 (HGNC:20185): (transmembrane protein 260) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM260 Gene-Disease associations (from GenCC):

• structural heart defects and renal anomalies syndrome

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 14-56585009-ATC-A is Pathogenic according to our data. Variant chr14-56585009-ATC-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 3337701.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017799.4. 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
	TMEM260	NM_017799.4	MANE Select	c.170_171delTC	p.Ile57AsnfsTer5	frameshift	Exon 2 of 16	NP_060269.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM260	ENST00000261556.11	TSL:2 MANE Select	c.170_171delTC	p.Ile57AsnfsTer5	frameshift	Exon 2 of 16	ENSP00000261556.6	Q9NX78-1
	TMEM260	ENST00000538838.5	TSL:1	c.170_171delTC	p.Ile57AsnfsTer5	frameshift	Exon 2 of 13	ENSP00000441934.1	Q9NX78-3
	TMEM260	ENST00000539559.6	TSL:1	n.170_171delTC		non_coding_transcript_exon	Exon 2 of 15	ENSP00000442602.2	F5H7D0

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr14-57051727;