Genetic Variant NM_005966.4:c.961T>C (chr2-190673108-T-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_005966.4(NAB1):c.961T>C(p.Cys321Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000187 in 1,606,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

NAB1
NM_005966.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.73

Publications

0 publications found

Variant links:

Genes affected

NAB1 (HGNC:7626): (NGFI-A binding protein 1) Predicted to enable transcription coregulator activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to act upstream of or within endochondral ossification; nervous system development; and regulation of epidermis development. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

NAB1 links:

ENSG00000228509 (HGNC:):

ENSG00000228509 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.41348645).

BS2

High AC in GnomAd4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005966.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAB1	NM_005966.4	MANE Select	c.961T>C	p.Cys321Arg	missense	Exon 6 of 10	NP_005957.2
NAB1	NM_001321312.2		c.961T>C	p.Cys321Arg	missense	Exon 4 of 8	NP_001308241.1	Q13506-1
NAB1	NM_001321313.1		c.961T>C	p.Cys321Arg	missense	Exon 4 of 8	NP_001308242.1	Q13506-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAB1	ENST00000337386.10	TSL:1 MANE Select	c.961T>C	p.Cys321Arg	missense	Exon 6 of 10	ENSP00000336894.5	Q13506-1
NAB1	ENST00000409641.5	TSL:1	c.961T>C	p.Cys321Arg	missense	Exon 3 of 7	ENSP00000386682.1	B8ZZS2
NAB1	ENST00000903121.1		c.994T>C	p.Cys332Arg	missense	Exon 4 of 8	ENSP00000573180.1

Frequencies

GnomAD3 genomes

AF:

0.0000397

AC:

AN:

150998

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000583

Gnomad SAS

AF:

0.000418

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000441

AC:

AN:

249626

AF XY:

0.0000370

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.000436

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000165

AC:

AN:

1455806

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

724414

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33284

American (AMR)

AF:

0.00

AC:

AN:

44526

Ashkenazi Jewish (ASJ)

AF:

0.0000768

AC:

AN:

26048

East Asian (EAS)

AF:

0.000354

AC:

AN:

39530

South Asian (SAS)

AF:

0.0000582

AC:

AN:

85928

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1108948

Other (OTH)

AF:

0.0000332

AC:

AN:

60172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000397

AC:

AN:

151112

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73812

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41128

American (AMR)

AF:

0.00

AC:

AN:

15136

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.000585

AC:

AN:

5132

South Asian (SAS)

AF:

0.000418

AC:

AN:

4780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10318

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67844

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

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:

0.00

Hom.:

ExAC

AF:

0.0000330

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

Pathogenic

0.62

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Pathogenic

0.26

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0063

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.90

PhyloP100

6.7

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.40

Sift

Uncertain

0.0090

Sift4G

Benign

0.48

Polyphen

0.97

Vest4

0.76

MVP

0.50

MPC

1.2

ClinPred

0.39

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.74

gMVP

0.37

Mutation Taster

=10/90

disease causing

(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