Variant 4-163129034-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_138386.3(NAF1):c.1348G>A(p.Gly450Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00736 in 1,393,560 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 3 hom., cov: 20)

Exomes 𝑓: 0.0077 ( 43 hom. )

Consequence

NAF1
NM_138386.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.233

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0061169863).

BP6

Variant 4-163129034-C-T is Benign according to our data. Variant chr4-163129034-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1336132.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 587 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAF1	NM_138386.3 linkuse as main transcript	c.1348G>A	p.Gly450Ser	missense_variant	8/8	ENST00000274054.3	NP_612395.2	Q96HR8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NAF1	ENST00000274054.3 linkuse as main transcript	c.1348G>A	p.Gly450Ser	missense_variant	8/8	1	NM_138386.3	ENSP00000274054.2	Q96HR8-1
NAF1	ENST00000422287.6 linkuse as main transcript	c.1034-1919G>A		intron_variant		1		ENSP00000408963.2	Q96HR8-2
NAF1	ENST00000509434.5 linkuse as main transcript	c.114+8165G>A		intron_variant		3		ENSP00000427518.1	D6RIB3

Frequencies

GnomAD3 genomes

AF:

0.00440

AC:

587

AN:

133440

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00342

Gnomad ASJ

AF:

0.000300

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000275

Gnomad FIN

AF:

0.000268

Gnomad MID

AF:

0.00333

Gnomad NFE

AF:

0.00753

Gnomad OTH

AF:

0.00381

GnomAD3 exomes

AF:

0.00389

AC:

581

AN:

149532

Hom.:

AF XY:

0.00388

AC XY:

312

AN XY:

80420

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00373

Gnomad ASJ exome

AF:

0.000242

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000896

Gnomad NFE exome

AF:

0.00777

Gnomad OTH exome

AF:

0.00835

GnomAD4 exome

AF:

0.00768

AC:

9674

AN:

1259996

Hom.:

Cov.:

AF XY:

0.00743

AC XY:

4602

AN XY:

619576

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.00448

Gnomad4 ASJ exome

AF:

0.000144

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000129

Gnomad4 FIN exome

AF:

0.00110

Gnomad4 NFE exome

AF:

0.00923

Gnomad4 OTH exome

AF:

0.00701

GnomAD4 genome

AF:

0.00439

AC:

587

AN:

133564

Hom.:

Cov.:

AF XY:

0.00400

AC XY:

256

AN XY:

63980

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.00341

Gnomad4 ASJ

AF:

0.000300

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000274

Gnomad4 FIN

AF:

0.000268

Gnomad4 NFE

AF:

0.00753

Gnomad4 OTH

AF:

0.00377

Alfa

AF:

0.00682

Hom.:

Bravo

AF:

0.00461

ESP6500AA

AF:

0.000968

AC:

ESP6500EA

AF:

0.00610

AC:

ExAC

AF:

0.00181

AC:

176

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2024	NAF1: BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.65

DEOGEN2

Benign

0.0085

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.41

M_CAP

Benign

0.014

MetaRNN

Benign

0.0061

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.24

REVEL

Benign

0.025

Sift

Benign

0.25

Sift4G

Benign

0.64

Polyphen

0.14

Vest4

0.081

MVP

0.30

MPC

0.080

ClinPred

0.0032

GERP RS

-0.65

Varity_R

0.029

gMVP

0.16

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

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