14-45210483-T-G

Variant names:

• chr14-45210483-T-G
• rs776009612
• NM_018353.5:c.3049A>C

Variant summary

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

The NM_018353.5(MIS18BP1):​c.3049A>C​(p.Asn1017His) 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 1,461,756 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. N1017D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MIS18BP1 NM_018353.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510
• Publications: 0 publications found

Genes affected

MIS18BP1 (HGNC:20190): (MIS18 binding protein 1) Predicted to enable DNA binding activity. Predicted to be involved in cell division. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.097322494).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018353.5. 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
	MIS18BP1	NM_018353.5	MANE Select	c.3049A>C	p.Asn1017His	missense	Exon 14 of 17	NP_060823.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIS18BP1	ENST00000310806.9	TSL:1 MANE Select	c.3049A>C	p.Asn1017His	missense	Exon 14 of 17	ENSP00000309790.4	Q6P0N0-1
	MIS18BP1	ENST00000919501.1		c.3094A>C	p.Asn1032His	missense	Exon 14 of 17	ENSP00000589560.1
	MIS18BP1	ENST00000901126.1		c.3049A>C	p.Asn1017His	missense	Exon 16 of 19	ENSP00000571185.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461756 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727184

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111936

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	10
DANN	Benign	0.85
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.051
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.13
Sift	Benign	0.071	T
Sift4G	Benign	0.29	T
Polyphen		0.91	P
Vest4		0.22
MutPred		0.20		Gain of catalytic residue at P1016 (P = 0.0068)
MVP		0.13
MPC		0.058
ClinPred		0.28	T
GERP RS		-4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.033
gMVP		0.076
Mutation Taster		=96/4	polymorphism

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: rs776009612; hg19: chr14-45679686;