Genetic Variant NPAT:c.*348A>T (chr11-108158594-T-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002519.3(NPAT):c.*348A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000792 in 184,262 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00082 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00065 ( 1 hom. )

Consequence

NPAT
NM_002519.3 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73

Publications

0 publications found

Variant links:

Genes affected

NPAT (HGNC:7896): (nuclear protein, coactivator of histone transcription) Enables protein C-terminus binding activity; transcription coactivator activity; and transcription corepressor activity. Involved in positive regulation of transcription by RNA polymerase II and regulation of transcription involved in G1/S transition of mitotic cell cycle. Located in Cajal body; Gemini of coiled bodies; and cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NPAT Gene-Disease associations (from GenCC):

colorectal cancer
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

NPAT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BS2

High AC in GnomAd4 at 125 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NPAT	NM_002519.3 link	c.*348A>T	3_prime_UTR_variant	Exon 18 of 18	ENST00000278612.9	NP_002510.2	Q14207
NPAT	NM_001321307.1 link	c.*348A>T	3_prime_UTR_variant	Exon 18 of 18		NP_001308236.1
NPAT	XM_011542854.3 link	c.*348A>T	3_prime_UTR_variant	Exon 18 of 18		XP_011541156.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NPAT	ENST00000278612.9 link	c.*348A>T	3_prime_UTR_variant	Exon 18 of 18	1	NM_002519.3	ENSP00000278612.8	Q14207
NPAT	ENST00000850623.1 link	c.*348A>T	3_prime_UTR_variant	Exon 18 of 18			ENSP00000520908.1
NPAT	ENST00000530859.1 link	n.*199A>T	downstream_gene_variant		2
NPAT	ENST00000530926.1 link	n.*44A>T	downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000822

AC:

125

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.0292

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.000479

GnomAD4 exome

AF:

0.000652

AC:

AN:

32188

Hom.:

Cov.:

AF XY:

0.000357

AC XY:

AN XY:

16812

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

350

American (AMR)

AF:

0.00

AC:

AN:

2240

Ashkenazi Jewish (ASJ)

AF:

0.0244

AC:

AN:

696

East Asian (EAS)

AF:

0.00

AC:

AN:

1290

South Asian (SAS)

AF:

0.00

AC:

AN:

4170

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1736

Middle Eastern (MID)

AF:

0.00

AC:

AN:

112

European-Non Finnish (NFE)

AF:

0.000201

AC:

AN:

19852

Other (OTH)

AF:

0.00

AC:

AN:

1742

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000822

AC:

125

AN:

152074

Hom.:

Cov.:

AF XY:

0.000687

AC XY:

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41432

American (AMR)

AF:

0.0000655

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.0292

AC:

101

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

67952

Other (OTH)

AF:

0.000479

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000971

Hom.:

Bravo

AF:

0.000790

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 02, 2019

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.0

(source)

DANN

Benign

0.45

PhyloP100

1.7

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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chr11-108158594-T-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over