rs1085307449

Variant names:

• chr14-56633141-GTATC-G
• rs1085307449
• NM_017799.4:c.1698_1701delCTAT

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.1698_1701delCTAT​(p.Tyr567ThrfsTer27) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM260 NM_017799.4 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:3
• Conservation: PhyloP100: 6.19
• Publications: 2 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

ENSG00000258428 (HGNC:):

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 14-56633141-GTATC-G is Pathogenic according to our data. Variant chr14-56633141-GTATC-G is described in ClinVar as Pathogenic. ClinVar VariationId is 426076.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.1698_1701delCTAT	p.Tyr567ThrfsTer27	frameshift	Exon 13 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.1698_1701delCTAT	p.Tyr567ThrfsTer27	frameshift	Exon 13 of 16	ENSP00000261556.6	Q9NX78-1
	TMEM260	ENST00000538838.5	TSL:1	c.*296_*299delCTAT		3_prime_UTR	Exon 12 of 13	ENSP00000441934.1	Q9NX78-3
	TMEM260	ENST00000539559.6	TSL:1	n.*608_*611delCTAT		non_coding_transcript_exon	Exon 12 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: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
3	-	-	Structural heart defects and renal anomalies syndrome (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.2
Mutation Taster		=6/194	disease causing (ClinVar)

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

dbSNP: rs1085307449; hg19: chr14-57099859;