NM_002139.4:c.1052C>T

Variant names:

• chrX-136874266-G-A
• rs760262374
• NM_002139.4:c.1052C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002139.4(RBMX):​c.1052C>T​(p.Pro351Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,098,086 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: RBMX NM_002139.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.99

Genes affected

RBMX (HGNC:9910): (RNA binding motif protein X-linked) This gene belongs to the RBMY gene family which includes candidate Y chromosome spermatogenesis genes. This gene, an active X chromosome homolog of the Y chromosome RBMY gene, is widely expressed whereas the RBMY gene evolved a male-specific function in spermatogenesis. Pseudogenes of this gene, found on chromosomes 1, 4, 9, 11, and 6, were likely derived by retrotransposition from the original gene. Alternatively spliced transcript variants encoding different isoforms have been identified. A snoRNA gene (SNORD61) is found in one of its introns. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32671988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBMX	NM_002139.4	c.1052C>T	p.Pro351Leu	missense_variant	Exon 9 of 9	ENST00000320676.11	NP_002130.2
RBMX	NM_001164803.2	c.540+820C>T		intron_variant	Intron 6 of 7		NP_001158275.1
RBMX	NR_028476.2	n.1035C>T		non_coding_transcript_exon_variant	Exon 8 of 8
RBMX	NR_028477.2	n.1242C>T		non_coding_transcript_exon_variant	Exon 9 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBMX	ENST00000320676.11	c.1052C>T	p.Pro351Leu	missense_variant	Exon 9 of 9	1	NM_002139.4	ENSP00000359645.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1098086 Hom.: 0 Cov.: 80 AF XY: 0.00 AC XY: 0 AN XY: 363568

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: 0.00000238

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.078	T;T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D;T
M_CAP	Pathogenic	0.57	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Uncertain	0.45
Sift	Benign	0.18	T;T
Sift4G	Benign	0.19	T;T
Polyphen		1.0	D;.
Vest4		0.28
MutPred		0.34		Loss of catalytic residue at P350 (P = 0.0175);.;
MVP		0.87
MPC		1.3
ClinPred		0.95	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.61

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

LitVar

Other links and lift over

dbSNP: rs760262374; hg19: chrX-135956425; COSMIC: COSV105209351; COSMIC: COSV105209351;