4-40432847-A-T

Position:

• chr4-40432847-A-T

Variant summary

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

The NM_001098634.2(RBM47):​c.1346T>A​(p.Ile449Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. I449T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBM47 NM_001098634.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.68

Genes affected

RBM47 (HGNC:30358): (RNA binding motif protein 47) Enables RNA binding activity. Predicted to act upstream of or within cytidine to uridine editing and hematopoietic progenitor cell differentiation. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM47	NM_001098634.2	c.1346T>A	p.Ile449Asn	missense_variant	6/7	ENST00000295971.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM47	ENST00000295971.12	c.1346T>A	p.Ile449Asn	missense_variant	6/7	5	NM_001098634.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2023

The c.1346T>A (p.I449N) alteration is located in exon 6 (coding exon 3) of the RBM47 gene. This alteration results from a T to A substitution at nucleotide position 1346, causing the isoleucine (I) at amino acid position 449 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;.;T;.
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.69	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	M;.;M;.
MutationTaster	Benign	1.0	D;D;D;N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.1	N;N;N;N
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D;T;D;D
Sift4G	Uncertain	0.047	D;T;D;T
Polyphen		0.85	P;P;P;.
Vest4		0.81
MutPred		0.58		Gain of phosphorylation at Y453 (P = 0.0798);.;Gain of phosphorylation at Y453 (P = 0.0798);.;
MVP		0.18
MPC		1.0
ClinPred		0.92	D
GERP RS		5.4
Varity_R		0.43
gMVP		0.90

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-40434864;