rs755353451

Variant names:

• chr2-190659798-C-G
• NM_005966.4:c.622C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-190659798-C-G
• chr2-190659798-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005966.4(NAB1):​c.622C>G​(p.Pro208Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,854 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P208S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NAB1 NM_005966.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.17

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10605961).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAB1	NM_005966.4	c.622C>G	p.Pro208Ala	missense_variant	Exon 4 of 10	ENST00000337386.10	NP_005957.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAB1	ENST00000337386.10	c.622C>G	p.Pro208Ala	missense_variant	Exon 4 of 10	1	NM_005966.4	ENSP00000336894.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461854 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727226

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.14	T;T;.
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.85	.;D;D
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L;L;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.62	N;N;N
REVEL	Benign	0.025
Sift	Benign	0.23	T;T;T
Sift4G	Benign	0.27	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.16
MutPred		0.28		Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);
MVP		0.20
MPC		0.26
ClinPred		0.28	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.044
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-191524524;