11-108158572-G-C

Variant names:

• chr11-108158572-G-C
• rs2134813735
• NM_002519.3:c.*370C>G

Variant summary

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

The NM_002519.3(NPAT):​c.*370C>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 0.0000528 in 18,930 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.000053 (0 hom.)
• Consequence: NPAT NM_002519.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• 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: 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=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAT	NM_002519.3	c.*370C>G		3_prime_UTR_variant	Exon 18 of 18	ENST00000278612.9	NP_002510.2
NPAT	NM_001321307.1	c.*370C>G		3_prime_UTR_variant	Exon 18 of 18		NP_001308236.1
NPAT	XM_011542854.3	c.*370C>G		3_prime_UTR_variant	Exon 18 of 18		XP_011541156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAT	ENST00000278612.9	c.*370C>G		3_prime_UTR_variant	Exon 18 of 18	1	NM_002519.3	ENSP00000278612.8
NPAT	ENST00000850623.1	c.*370C>G		3_prime_UTR_variant	Exon 18 of 18			ENSP00000520908.1
NPAT	ENST00000530859.1	n.*221C>G		downstream_gene_variant		2
NPAT	ENST00000530926.1	n.*66C>G		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000528 AC: 1 AN: 18930 Hom.: 0 Cov.: 0 AF XY: 0.000102 AC XY: 1 AN XY: 9832

African (AFR) AF: 0.00 AC: 0 AN: 174

American (AMR) AF: 0.00 AC: 0 AN: 1666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 354

East Asian (EAS) AF: 0.00 AC: 0 AN: 686

South Asian (SAS) AF: 0.00 AC: 0 AN: 2090

European-Finnish (FIN) AF: 0.000876 AC: 1 AN: 1142

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 60

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 11728

Other (OTH) AF: 0.00 AC: 0 AN: 1030

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.8
DANN	Benign	0.57
PhyloP100		1.3

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: rs2134813735; hg19: chr11-108029299;