rs776937673

Variant names:

• chr16-10744021-A-C
• rs776937673
• NM_002484.4:c.80A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-10744021-A-C
• chr16-10744021-A-G
• chr16-10744021-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002484.4(NUBP1):​c.80A>C​(p.Asn27Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000014 in 1,428,028 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N27S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NUBP1 NM_002484.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.78
• Publications: 0 publications found

Genes affected

NUBP1 (HGNC:8041): (NUBP iron-sulfur cluster assembly factor 1, cytosolic) NUBP1 is a member of the NUBP/MRP subfamily of ATP-binding proteins (Nakashima et al., 1999 [PubMed 10486206]).[supplied by OMIM, Mar 2008]

ENSG00000289073 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002484.4. 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
	NUBP1	NM_002484.4	MANE Select	c.80A>C	p.Asn27Thr	missense	Exon 2 of 11	NP_002475.2	P53384-1
	NUBP1	NM_001278506.2		c.80A>C	p.Asn27Thr	missense	Exon 2 of 10	NP_001265435.1	P53384-2
	NUBP1	NM_001323595.2		c.80A>C	p.Asn27Thr	missense	Exon 2 of 10	NP_001310524.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUBP1	ENST00000283027.10	TSL:1 MANE Select	c.80A>C	p.Asn27Thr	missense	Exon 2 of 11	ENSP00000283027.5	P53384-1
	NUBP1	ENST00000433392.6	TSL:1	c.80A>C	p.Asn27Thr	missense	Exon 2 of 10	ENSP00000409654.2	P53384-2
	NUBP1	ENST00000571790.5	TSL:1	n.103A>C		non_coding_transcript_exon	Exon 2 of 10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1428028 Hom.: 0 Cov.: 32 AF XY: 0.00000141 AC XY: 1 AN XY: 710078

African (AFR) AF: 0.00 AC: 0 AN: 31252

American (AMR) AF: 0.00 AC: 0 AN: 35768

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24868

East Asian (EAS) AF: 0.00 AC: 0 AN: 37612

South Asian (SAS) AF: 0.00 AC: 0 AN: 81406

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51718

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5622

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1100934

Other (OTH) AF: 0.00 AC: 0 AN: 58848

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

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	0.60
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.085	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.8
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.24
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.022	D
Polyphen		1.0	D
Vest4		0.66
MutPred		0.22		Gain of catalytic residue at N27 (P = 0.0325)
MVP		0.64
MPC		0.12
ClinPred		1.0	D
GERP RS		4.1
PromoterAI		-0.042	Neutral
Varity_R		0.91
gMVP		0.49
Mutation Taster		=9/91	disease causing

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

Other links and lift over

dbSNP: rs776937673; hg19: chr16-10837878;