Genetic Variant NM_001369441.2:c.470A>G (chr2-200893279-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001369441.2(NIF3L1):c.470A>G(p.Lys157Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000183 in 1,573,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

NIF3L1
NM_001369441.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.430

Publications

4 publications found

Variant links:

Genes affected

NIF3L1 (HGNC:13390): (NGG1 interacting factor 3 like 1) Enables identical protein binding activity. Involved in positive regulation of transcription, DNA-templated. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NIF3L1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04820302).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369441.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NIF3L1	NM_001369441.2	MANE Select	c.470A>G	p.Lys157Arg	missense	Exon 3 of 7	NP_001356370.1	Q9GZT8-1
NIF3L1	NM_001136039.2		c.470A>G	p.Lys157Arg	missense	Exon 3 of 7	NP_001129511.1	Q9GZT8-1
NIF3L1	NM_001369442.1		c.470A>G	p.Lys157Arg	missense	Exon 3 of 7	NP_001356371.1	Q9GZT8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NIF3L1	ENST00000409020.6	TSL:5 MANE Select	c.470A>G	p.Lys157Arg	missense	Exon 3 of 7	ENSP00000386394.1	Q9GZT8-1
NIF3L1	ENST00000359683.8	TSL:1	c.389A>G	p.Lys130Arg	missense	Exon 3 of 7	ENSP00000352711.4	Q9GZT8-2
NIF3L1	ENST00000409588.1	TSL:1	c.470A>G	p.Lys157Arg	missense	Exon 2 of 5	ENSP00000387021.1	Q9GZT8-3

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

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:

0.000235

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000115

AC:

AN:

225208

AF XY:

0.000138

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000249

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000186

AC:

265

AN:

1421346

Hom.:

Cov.:

AF XY:

0.000197

AC XY:

139

AN XY:

704750

show subpopulations

African (AFR)

AF:

0.0000966

AC:

AN:

31050

American (AMR)

AF:

0.0000510

AC:

AN:

39228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24764

East Asian (EAS)

AF:

0.00

AC:

AN:

37584

South Asian (SAS)

AF:

0.00

AC:

AN:

82056

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52764

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5588

European-Non Finnish (NFE)

AF:

0.000234

AC:

255

AN:

1090008

Other (OTH)

AF:

0.0000858

AC:

AN:

58304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000151

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41414

American (AMR)

AF:

0.000328

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000367

AC:

ExAC

AF:

0.0000745

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.65

CADD

Benign

9.0

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.034

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.65

M_CAP

Benign

0.0046

MetaRNN

Benign

0.048

MetaSVM

Benign

-1.0

PhyloP100

-0.43

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.34

REVEL

Benign

0.058

Sift

Benign

0.49

Sift4G

Benign

0.54

Polyphen

0.0010

Vest4

0.14

MVP

0.30

MPC

0.040

ClinPred

0.022

GERP RS

-3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.044

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over