chr16-10744050-G-T

Variant names:

• chr16-10744050-G-T
• rs566213410
• NM_002484.4:c.109G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002484.4(NUBP1):​c.109G>T​(p.Ala37Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000014 in 1,429,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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: 5.67
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17852297).

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.109G>T	p.Ala37Ser	missense	Exon 2 of 11	NP_002475.2	P53384-1
	NUBP1	NM_001278506.2		c.109G>T	p.Ala37Ser	missense	Exon 2 of 10	NP_001265435.1	P53384-2
	NUBP1	NM_001323595.2		c.109G>T	p.Ala37Ser	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.109G>T	p.Ala37Ser	missense	Exon 2 of 11	ENSP00000283027.5	P53384-1
	NUBP1	ENST00000433392.6	TSL:1	c.109G>T	p.Ala37Ser	missense	Exon 2 of 10	ENSP00000409654.2	P53384-2
	NUBP1	ENST00000571790.5	TSL:1	n.132G>T		non_coding_transcript_exon	Exon 2 of 10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1429342 Hom.: 0 Cov.: 32 AF XY: 0.00000141 AC XY: 1 AN XY: 710352

African (AFR) AF: 0.00 AC: 0 AN: 31722

American (AMR) AF: 0.00 AC: 0 AN: 36576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25050

East Asian (EAS) AF: 0.00 AC: 0 AN: 38042

South Asian (SAS) AF: 0.00 AC: 0 AN: 81258

European-Finnish (FIN) AF: 0.0000196 AC: 1 AN: 51094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5482

European-Non Finnish (NFE) AF: 9.08e-7 AC: 1 AN: 1101194

Other (OTH) AF: 0.00 AC: 0 AN: 58924

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	Benign	0.085
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		5.7
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.050
Sift	Benign	0.15	T
Sift4G	Benign	0.67	T
Polyphen		0.0010	B
Vest4		0.24
MutPred		0.25		Gain of glycosylation at A37 (P = 0.0088)
MVP		0.49
MPC		0.019
ClinPred		0.59	D
GERP RS		3.8
PromoterAI		-0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.099
gMVP		0.70

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: rs566213410; hg19: chr16-10837907;