2-237817208-A-G

Position:

• chr2-237817208-A-G

Variant summary

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

The NM_001080504.3(RBM44):​c.289A>G​(p.Ser97Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,538 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RBM44 NM_001080504.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.541

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]

RBM44 (HGNC:):

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=0.0906001).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM44	NM_001080504.3	c.289A>G	p.Ser97Gly	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.289A>G	p.Ser97Gly	missense_variant	3/16	5	NM_001080504.3	ENSP00000321179.5
RBM44	ENST00000409864.6	c.289A>G	p.Ser97Gly	missense_variant	3/15	5		ENSP00000386727.2
RBM44	ENST00000480583.5	n.780A>G		non_coding_transcript_exon_variant	3/15	2
RBM44	ENST00000444524.2	n.202-2967A>G		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449538 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 721080

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.03e-7

Gnomad4 OTH exome AF: 0.00

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 19, 2022

The c.292A>G (p.S98G) alteration is located in exon 3 (coding exon 2) of the RBM44 gene. This alteration results from a A to G substitution at nucleotide position 292, causing the serine (S) at amino acid position 98 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	0.071
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	8.4
DANN	Benign	0.93
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.38	T;.
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.091	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.91	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.086
Sift	Benign	0.13	T;T
Sift4G	Benign	0.25	T;T
Vest4		0.12
MVP		0.29
MPC		0.021
ClinPred		0.35	T
GERP RS		3.1
gMVP		0.065

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr2-238725851;