X-53430940-T-A

Position:

• chrX-53430940-T-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001031745.5(RIBC1):​c.1092T>A​(p.Asn364Lys) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: RIBC1 NM_001031745.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0840

Genes affected

RIBC1 (HGNC:26537): (RIB43A domain with coiled-coils 1)

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.95

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIBC1	NM_001031745.5	c.1092T>A	p.Asn364Lys	missense_variant	8/8	ENST00000375327.6	NP_001026915.1
RIBC1	XM_005261988.5	c.1092T>A	p.Asn364Lys	missense_variant	8/8		XP_005262045.1
RIBC1	XM_005261990.5	c.747T>A	p.Asn249Lys	missense_variant	7/7		XP_005262047.1
RIBC1	NM_001267053.4	c.*146T>A		3_prime_UTR_variant	6/6		NP_001253982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIBC1	ENST00000375327.6	c.1092T>A	p.Asn364Lys	missense_variant	8/8	1	NM_001031745.5	ENSP00000364476	P1
RIBC1	ENST00000414955.6	c.*146T>A		3_prime_UTR_variant	6/6	2		ENSP00000401463

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.11e-7 AC: 1 AN: 1098032 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 1 AN XY: 363386

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: 0.0000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jun 13, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (Richards et al., 2015) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.65	T
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Benign	-0.53	T
MutationAssessor	Pathogenic	3.1	M
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.33
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.73
MutPred		0.85		Gain of methylation at N364 (P = 0.0051);
MVP		0.45
MPC		0.86
ClinPred		0.99	D
GERP RS		2.9
Varity_R		0.90
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chrX-53457888;