chr7-128317664-T-C

Position:

• chr7-128317664-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018077.3(RBM28):​c.1783A>G​(p.Ser595Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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)
• Consequence: RBM28 NM_018077.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.20

Genes affected

RBM28 (HGNC:21863): (RNA binding motif protein 28) The protein encoded by this gene is a specific nucleolar component of the spliceosomal small nuclear ribonucleoprotein (snRNP)complexes . It specifically associates with U1, U2, U4, U5, and U6 small nuclear RNAs (snRNAs), possibly coordinating their transition through the nucleolus. Mutation in this gene causes alopecia, progressive neurological defects, and endocrinopathy (ANE syndrome), a pleiotropic and clinically heterogeneous disorder. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14454451).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM28	NM_018077.3	c.1783A>G	p.Ser595Gly	missense_variant	16/19	ENST00000223073.6
RBM28	NM_001166135.2	c.1360A>G	p.Ser454Gly	missense_variant	12/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM28	ENST00000223073.6	c.1783A>G	p.Ser595Gly	missense_variant	16/19	1	NM_018077.3	P1
RBM28	ENST00000415472.6	c.1360A>G	p.Ser454Gly	missense_variant	12/15	2
RBM28	ENST00000481788.1	n.161-2644A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Apr 29, 2024

The c.1783A>G (p.S595G) alteration is located in exon 16 (coding exon 16) of the RBM28 gene. This alteration results from a A to G substitution at nucleotide position 1783, causing the serine (S) at amino acid position 595 to be replaced by a glycine (G). 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	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T;.
Eigen	Benign	0.088
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.
MutationTaster	Benign	0.97	D;D
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.065
Sift	Benign	0.034	D;D
Sift4G	Benign	0.35	T;T
Polyphen		0.45	B;.
Vest4		0.21
MutPred		0.23		Loss of phosphorylation at S595 (P = 0.0162);.;
MVP		0.19
MPC		0.24
ClinPred		0.81	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr7-127957717;