16-10744053-A-C

Variant names:

• chr16-10744053-A-C
• rs748563539
• NM_002484.4:c.112A>C

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.112A>C​(p.Thr38Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. T38A) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: NUBP1 NM_002484.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43
• 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=0.10962698).

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.112A>C	p.Thr38Pro	missense	Exon 2 of 11	NP_002475.2	P53384-1
	NUBP1	NM_001278506.2		c.112A>C	p.Thr38Pro	missense	Exon 2 of 10	NP_001265435.1	P53384-2
	NUBP1	NM_001323595.2		c.112A>C	p.Thr38Pro	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.112A>C	p.Thr38Pro	missense	Exon 2 of 11	ENSP00000283027.5	P53384-1
	NUBP1	ENST00000433392.6	TSL:1	c.112A>C	p.Thr38Pro	missense	Exon 2 of 10	ENSP00000409654.2	P53384-2
	NUBP1	ENST00000571790.5	TSL:1	n.135A>C		non_coding_transcript_exon	Exon 2 of 10

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151586 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000952

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151586 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 73982

African (AFR) AF: 0.00 AC: 0 AN: 41186

American (AMR) AF: 0.00 AC: 0 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.0000952 AC: 1 AN: 10500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67948

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	14
DANN	Benign	0.67
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.5	N
PhyloP100		2.4
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.032
Sift	Benign	0.14	T
Sift4G	Benign	0.31	T
Polyphen		0.0	B
Vest4		0.25
MutPred		0.29		Gain of loop (P = 0.0079)
MVP		0.23
MPC		0.020
ClinPred		0.13	T
GERP RS		-2.1
PromoterAI		0.029	Neutral
Varity_R		0.10
gMVP		0.59

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: rs748563539; hg19: chr16-10837910;