rs1343688414

Variant names:

• chrX-153935300-G-A
• rs1343688414
• NM_002910.6:c.1270C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-153935300-G-A
• chrX-153935300-G-C
• chrX-153935300-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002910.6(RENBP):​c.1270C>T​(p.Arg424*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000127 in 786,106 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000013 (0 hom. 0 hem.)
• Consequence: RENBP NM_002910.6 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.57
• Publications: 0 publications found

Genes affected

RENBP (HGNC:9959): (renin binding protein) The gene product inhibits renin activity by forming a dimer with renin, a complex known as high molecular weight renin. The encoded protein contains a leucine zipper domain, which is essential for its dimerization with renin. The gene product can catalyze the interconversion of N-acetylglucosamine to N-acetylmannosamine, indicating that it is a GlcNAc 2-epimerase. Transcript variants utilizing alternative promoters have been described in the literature. [provided by RefSeq, Jul 2008]

NAA10 (HGNC:18704): (N-alpha-acetyltransferase 10, NatA catalytic subunit) N-alpha-acetylation is among the most common post-translational protein modifications in eukaryotic cells. This process involves the transfer of an acetyl group from acetyl-coenzyme A to the alpha-amino group on a nascent polypeptide and is essential for normal cell function. This gene encodes an N-terminal acetyltransferase that functions as the catalytic subunit of the major amino-terminal acetyltransferase A complex. Mutations in this gene are the cause of Ogden syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]

NAA10 Gene-Disease associations (from GenCC):

• microphthalmia, syndromic 1

  Inheritance: XL, Unknown Classification: DEFINITIVE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• NAA10-related syndrome

  Inheritance: XL Classification: DEFINITIVE Submitted by: Broad Center for Mendelian Genomics, ClinGen, G2P
• Ogden syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• microphthalmia, Lenz type

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002910.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RENBP	NM_002910.6	MANE Select	c.1270C>T	p.Arg424*	stop_gained	Exon 11 of 11	NP_002901.2	P51606-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RENBP	ENST00000393700.8	TSL:1 MANE Select	c.1270C>T	p.Arg424*	stop_gained	Exon 11 of 11	ENSP00000377303.3	P51606-1
	RENBP	ENST00000875215.1		c.1396C>T	p.Arg466*	stop_gained	Exon 12 of 12	ENSP00000545274.1
	RENBP	ENST00000369997.7	TSL:5	c.1228C>T	p.Arg410*	stop_gained	Exon 11 of 11	ENSP00000359014.3	A6NKZ2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000127 AC: 1 AN: 786106 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 196130

African (AFR) AF: 0.00 AC: 0 AN: 16472

American (AMR) AF: 0.00 AC: 0 AN: 10713

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11750

East Asian (EAS) AF: 0.00 AC: 0 AN: 22308

South Asian (SAS) AF: 0.00 AC: 0 AN: 30390

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2044

European-Non Finnish (NFE) AF: 0.00000158 AC: 1 AN: 632132

Other (OTH) AF: 0.00 AC: 0 AN: 34203

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	23
DANN	Benign	0.86
FATHMM_MKL	Benign	0.022	N
PhyloP100		-2.6
Vest4		0.48
GERP RS		-3.0
PromoterAI		-0.017	Neutral
Mutation Taster		=160/40	polymorphism

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

Other links and lift over

dbSNP: rs1343688414; hg19: chrX-153200753;