2-237817085-T-A

Position:

• chr2-237817085-T-A

Variant summary

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

The NM_001080504.3(RBM44):​c.166T>A​(p.Ser56Thr) 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. 14/19 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: RBM44 NM_001080504.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.468

Genes affected

RBM44 (HGNC:24756): (RNA binding motif protein 44) Predicted to enable protein homodimerization activity. Predicted to be located in cytoplasm and intercellular bridge. [provided by Alliance of Genome Resources, Apr 2022]

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=0.1506123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM44	NM_001080504.3	c.166T>A	p.Ser56Thr	missense_variant	3/16	ENST00000316997.9	NP_001073973.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM44	ENST00000316997.9	c.166T>A	p.Ser56Thr	missense_variant	3/16	5	NM_001080504.3	ENSP00000321179	P1
RBM44	ENST00000409864.6	c.166T>A	p.Ser56Thr	missense_variant	3/15	5		ENSP00000386727	P1
RBM44	ENST00000480583.5	n.657T>A		non_coding_transcript_exon_variant	3/15	2
RBM44	ENST00000444524.2	n.202-3090T>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Dec 02, 2022

The c.169T>A (p.S57T) alteration is located in exon 3 (coding exon 2) of the RBM44 gene. This alteration results from a T to A substitution at nucleotide position 169, causing the serine (S) at amino acid position 57 to be replaced by a threonine (T). 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	0.087
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	13
DANN	Benign	0.77
Eigen	Benign	-0.087
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.37	T;.
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.94	N;N
REVEL	Benign	0.12
Sift	Benign	0.097	T;T
Sift4G	Benign	0.12	T;T
Vest4		0.28
MVP		0.37
MPC		0.030
ClinPred		0.27	T
GERP RS		4.3
gMVP		0.083

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-238725728;