1-88982871-C-G

Position:

• chr1-88982871-C-G

Variant summary

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

The ENST00000260508.9(KYAT3):​c.99+5381G>C variant causes a intron change. The variant allele was found at a frequency of 0.00000372 in 1,613,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: KYAT3 ENST00000260508.9 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.42

Genes affected

RBMXL1 (HGNC:25073): (RBMX like 1) This gene represents a retrogene of RNA binding motif protein, X-linked (RBMX), which is located on chromosome X. While all introns in the coding sequence have been processed out compared to the RBMX locus, the ORF is intact and there is specific evidence for transcription at this location. The preservation of the ORF by purifying selection in all Old World monkeys carrying it suggests that this locus is likely to be functional, possibly during male meiosis when X chromosomal genes are silenced or during haploid stages of spermatogenesis. This gene shares 5' exon structure with the cysteine conjugate-beta lyase 2 locus on chromosome 1, but the coding sequences are non-overlapping. Alternative splicing results in two transcript variants. [provided by RefSeq, Jun 2009]

KYAT3 (HGNC:33238): (kynurenine aminotransferase 3) This gene encodes an aminotransferase that transaminates kynurenine to form kynurenic acid, which is a metabolite of tryptophan. Multiple alternatively spliced transcript variants that encode different proteins have been described for this gene. This gene shares 5' exon structure with the RNA binding motif protein, X-linked-like 1 locus on chromosome 1, but the coding sequences are non-overlapping. [provided by RefSeq, Mar 2017]

KYAT3 (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=0.14363047).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBMXL1	NM_001162536.3	c.956G>C	p.Gly319Ala	missense_variant	3/3	ENST00000652648.1	NP_001156008.1
KYAT3	NM_001008661.3	c.99+5381G>C		intron_variant		ENST00000260508.9	NP_001008661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBMXL1	ENST00000652648.1	c.956G>C	p.Gly319Ala	missense_variant	3/3		NM_001162536.3	ENSP00000498248.1
KYAT3	ENST00000260508.9	c.99+5381G>C		intron_variant		1	NM_001008661.3	ENSP00000260508.4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461672 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727146

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: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74346

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

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

Nov 08, 2021

The c.956G>C (p.G319A) alteration is located in exon 3 (coding exon 1) of the RBMXL1 gene. This alteration results from a G to C substitution at nucleotide position 956, causing the glycine (G) at amino acid position 319 to be replaced by an alanine (A). 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	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	14
DANN	Benign	0.92
DEOGEN2	Benign	0.0064	T;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.73	.;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.1	L;L
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.81	N;N
REVEL	Benign	0.29
Sift	Benign	0.41	T;T
Sift4G	Benign	0.99	T;T
Polyphen		0.73	P;P
Vest4		0.14
MutPred		0.098		Gain of methylation at R324 (P = 0.1391);Gain of methylation at R324 (P = 0.1391);
MVP		0.68
MPC		0.62
ClinPred		0.51	D
GERP RS		1.9
Varity_R		0.055
gMVP		0.11

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: rs1677176276; hg19: chr1-89448554;