Genetic Variant NET1:c.595-56A>T (chr10-5453194-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.354

Publications

11 publications found

Variant links:

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]

NET1 links:

ENSG00000288922 (HGNC:):

ENSG00000288922 links:

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ACMG classification

Classification was made for transcript

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NET1	NM_001047160.3 link	c.595-56A>T	intron_variant	Intron 6 of 11	ENST00000355029.9	NP_001040625.1	Q7Z628-1Q5SQI5
NET1	NM_005863.5 link	c.433-56A>T	intron_variant	Intron 4 of 9		NP_005854.2	Q7Z628-2Q5SQI7
NET1	NR_073040.1 link	n.681-56A>T	intron_variant	Intron 4 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NET1	ENST00000355029.9 link	c.595-56A>T		intron_variant	Intron 6 of 11	1	NM_001047160.3	ENSP00000347134.4		Q7Z628-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

829032

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

437832

African (AFR)

AF:

0.00

AC:

AN:

21212

American (AMR)

AF:

0.00

AC:

AN:

42668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21920

East Asian (EAS)

AF:

0.00

AC:

AN:

36860

South Asian (SAS)

AF:

0.00

AC:

AN:

72710

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52960

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4462

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

536822

Other (OTH)

AF:

0.00

AC:

AN:

39418

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

22679

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.17

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over