10-5453194-A-T

Variant names:

• chr10-5453194-A-T
• rs11253185
• NM_001047160.3:c.595-56A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001047160.3(NET1):​c.595-56A>T variant causes a intron 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NET1 NM_001047160.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.354
• Publications: 11 publications found

Genes affected

NET1 (HGNC:14592): (neuroepithelial cell transforming 1) This gene is part of the family of Rho guanine nucleotide exchange factors. Members of this family activate Rho proteins by catalyzing the exchange of GDP for GTP. The protein encoded by this gene interacts with RhoA within the cell nucleus and may play a role in repairing DNA damage after ionizing radiation. Pseudogenes of this gene are located on the long arms of chromosomes 1, 7 and 18. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

ENSG00000288922 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001047160.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NET1	NM_001047160.3	MANE Select	c.595-56A>T		intron	N/A	NP_001040625.1
	NET1	NM_005863.5		c.433-56A>T		intron	N/A	NP_005854.2
	NET1	NR_073040.1		n.681-56A>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NET1	ENST00000355029.9	TSL:1 MANE Select	c.595-56A>T		intron	N/A	ENSP00000347134.4
	NET1	ENST00000380359.3	TSL:1	c.433-56A>T		intron	N/A	ENSP00000369717.3
	NET1	ENST00000449083.5	TSL:5	c.94-101A>T		intron	N/A	ENSP00000403101.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 829032 Hom.: 0 Cov.: 11 AF XY: 0.00 AC XY: 0 AN XY: 437832

African (AFR) AF: 0.00 AC: 0 AN: 21212

American (AMR) AF: 0.00 AC: 0 AN: 42668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21920

East Asian (EAS) AF: 0.00 AC: 0 AN: 36860

South Asian (SAS) AF: 0.00 AC: 0 AN: 72710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4462

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 536822

Other (OTH) AF: 0.00 AC: 0 AN: 39418

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 22679

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.17
DANN	Benign	0.50
PhyloP100		-0.35

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: rs11253185; hg19: chr10-5495157;