chr2-190673108-T-C

Variant names:

• chr2-190673108-T-C
• rs200990302
• NM_005966.4:c.961T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.73
• Publications: 0 publications found

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]

ENSG00000228509 (HGNC:):

ACMG classification

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

Sel.	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

Sel.	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: 6 AN: 150998 Hom.: 0 Cov.: 31

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: 11 AN: 249626 AF XY: 0.0000370

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: 24 AN: 1455806 Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8 AN XY: 724414

African (AFR) AF: 0.00 AC: 0 AN: 33284

American (AMR) AF: 0.00 AC: 0 AN: 44526

Ashkenazi Jewish (ASJ) AF: 0.0000768 AC: 2 AN: 26048

East Asian (EAS) AF: 0.000354 AC: 14 AN: 39530

South Asian (SAS) AF: 0.0000582 AC: 5 AN: 85928

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108948

Other (OTH) AF: 0.0000332 AC: 2 AN: 60172

GnomAD4 genome AF: 0.0000397 AC: 6 AN: 151112 Hom.: 0 Cov.: 31 AF XY: 0.0000271 AC XY: 2 AN XY: 73812

African (AFR) AF: 0.00 AC: 0 AN: 41128

American (AMR) AF: 0.00 AC: 0 AN: 15136

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.000585 AC: 3 AN: 5132

South Asian (SAS) AF: 0.000418 AC: 2 AN: 4780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67844

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Pathogenic	0.26
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.90	L
PhyloP100		6.7
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.48	T
Polyphen		0.97	D
Vest4		0.76
MVP		0.50
MPC		1.2
ClinPred		0.39	T
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

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

Other links and lift over

dbSNP: rs200990302; hg19: chr2-191537834;