Variant 4-163127016-G-GT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PVS1_ModeratePP5BS2

The NM_001128931.2(NAF1):c.1132dupA(p.Thr378fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000413 in 1,551,358 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely risk allele (no stars).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

NAF1
NM_001128931.2 frameshift

Scores

Not classified

Clinical Significance

Likely risk allele no assertion criteria provided P:1

Conservation

PhyloP100: 0.308

Variant links:

Genes affected

NAF1 (HGNC:25126): (nuclear assembly factor 1 ribonucleoprotein) Enables identical protein binding activity and telomerase RNA binding activity. Involved in regulation of nucleobase-containing compound metabolic process; ribosome biogenesis; and telomerase holoenzyme complex assembly. Located in nucleoplasm. Part of sno(s)RNA-containing ribonucleoprotein complex. [provided by Alliance of Genome Resources, Apr 2022]

NAF1 links:

NAF1 (HGNC:):

NAF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0325 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

PP5

Variant 4-163127016-G-GT is Pathogenic according to our data. Variant chr4-163127016-G-GT is described in ClinVar as [Likely_risk_allele]. Clinvar id is 1695920.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_pathogenic, oryginal submission is: [Likely_risk_allele].

BS2

High AC in GnomAd4 at 34 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
NAF1	NM_001128931.2 linkuse as main transcript	c.1132dupA	p.Thr378fs	frameshift_variant	8/8	NP_001122403.1	Q96HR8-2
NAF1	XM_011532410.4 linkuse as main transcript	c.*144dupA		3_prime_UTR_variant	9/9	XP_011530712.1	Q96HR8-1
NAF1	XR_001741349.3 linkuse as main transcript	n.1747+45dupA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAF1	ENST00000422287.6 linkuse as main transcript	c.1132dupA	p.Thr378fs	frameshift_variant	8/8	1		ENSP00000408963.2		Q96HR8-2
NAF1	ENST00000509434.5 linkuse as main transcript	c.114+10182dupA		intron_variant		3		ENSP00000427518.1		D6RIB3

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000462

AC:

AN:

151364

Hom.:

AF XY:

0.0000497

AC XY:

AN XY:

80484

show subpopulations

Gnomad AFR exome

AF:

0.000379

Gnomad AMR exome

AF:

0.0000811

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000918

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000175

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000214

AC:

AN:

1399198

Hom.:

Cov.:

AF XY:

0.0000217

AC XY:

AN XY:

690108

show subpopulations

Gnomad4 AFR exome

AF:

0.000633

Gnomad4 AMR exome

AF:

0.0000841

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000371

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.000223

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.000652

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000283

ClinVar

Significance: Likely risk allele

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Pulmonary fibrosis

Pathogenic:1

Likely risk allele, no assertion criteria provided

research

Garcia Pulmonary Genetics Research Laboratory, Columbia University Irving Medical Center

Jun 09, 2022

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over