11-108157939-T-C

Variant names:

• chr11-108157939-T-C
• rs556765145
• NM_002519.3:c.*1003A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002519.3(NPAT):​c.*1003A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000302 in 152,192 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00030 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPAT NM_002519.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.09
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-108157939-T-C is Benign according to our data. Variant chr11-108157939-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1337453.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 46 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002519.3. 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
	NPAT	NM_002519.3	MANE Select	c.*1003A>G		3_prime_UTR	Exon 18 of 18	NP_002510.2	Q14207
	NPAT	NM_001321307.1		c.*1003A>G		3_prime_UTR	Exon 18 of 18	NP_001308236.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAT	ENST00000278612.9	TSL:1 MANE Select	c.*1003A>G		3_prime_UTR	Exon 18 of 18	ENSP00000278612.8	Q14207
	NPAT	ENST00000935790.1		c.*1003A>G		3_prime_UTR	Exon 18 of 18	ENSP00000605849.1
	NPAT	ENST00000850623.1		c.*1003A>G		3_prime_UTR	Exon 18 of 18	ENSP00000520908.1	Q14207

Frequencies

GnomAD3 genomes AF: 0.000302 AC: 46 AN: 152074 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.000480

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 432 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.000302 AC: 46 AN: 152192 Hom.: 1 Cov.: 32 AF XY: 0.000390 AC XY: 29 AN XY: 74414

African (AFR) AF: 0.0000241 AC: 1 AN: 41564

American (AMR) AF: 0.000131 AC: 2 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00720 AC: 25 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67932

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.000693 Hom.: 0

Bravo AF: 0.000291

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.23
DANN	Benign	0.64
PhyloP100		-2.1

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: rs556765145; hg19: chr11-108028666;