chrX-153935307-G-A

Variant names:

• chrX-153935307-G-A
• rs781854646
• NM_002910.6:c.1263C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002910.6(RENBP):​c.1263C>T​(p.Pro421Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00058 in 914,749 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 130 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., 10 hem., cov: 23)
  • Exomes 𝑓: 0.00060 (0 hom. 120 hem.)
• Consequence: RENBP NM_002910.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0600
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant X-153935307-G-A is Benign according to our data. Variant chrX-153935307-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2661762.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.06 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 10 gene

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.1263C>T	p.Pro421Pro	synonymous	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.1263C>T	p.Pro421Pro	synonymous	Exon 11 of 11	ENSP00000377303.3	P51606-1
	RENBP	ENST00000875215.1		c.1389C>T	p.Pro463Pro	synonymous	Exon 12 of 12	ENSP00000545274.1
	RENBP	ENST00000369997.7	TSL:5	c.1221C>T	p.Pro407Pro	synonymous	Exon 11 of 11	ENSP00000359014.3	A6NKZ2

Frequencies

GnomAD3 genomes AF: 0.000435 AC: 48 AN: 110391 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000983

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000943

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: 0.000824

Gnomad OTH AF: 0.000669

GnomAD2 exomes AF: 0.000485 AC: 9 AN: 18543 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00125

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000600 AC: 483 AN: 804358 Hom.: 0 Cov.: 12 AF XY: 0.000585 AC XY: 120 AN XY: 205198

African (AFR) AF: 0.000118 AC: 2 AN: 16902

American (AMR) AF: 0.000185 AC: 2 AN: 10798

Ashkenazi Jewish (ASJ) AF: 0.0000843 AC: 1 AN: 11863

East Asian (EAS) AF: 0.00 AC: 0 AN: 22402

South Asian (SAS) AF: 0.00 AC: 0 AN: 30721

European-Finnish (FIN) AF: 0.0000369 AC: 1 AN: 27087

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2071

European-Non Finnish (NFE) AF: 0.000722 AC: 468 AN: 647812

Other (OTH) AF: 0.000259 AC: 9 AN: 34702

GnomAD4 genome AF: 0.000435 AC: 48 AN: 110391 Hom.: 0 Cov.: 23 AF XY: 0.000305 AC XY: 10 AN XY: 32801

African (AFR) AF: 0.0000983 AC: 3 AN: 30527

American (AMR) AF: 0.0000943 AC: 1 AN: 10603

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2623

East Asian (EAS) AF: 0.00 AC: 0 AN: 3480

South Asian (SAS) AF: 0.00 AC: 0 AN: 2709

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5864

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 234

European-Non Finnish (NFE) AF: 0.000824 AC: 43 AN: 52186

Other (OTH) AF: 0.000669 AC: 1 AN: 1494

Alfa AF: 0.000674 Hom.: 2

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.9
DANN	Benign	0.82
PhyloP100		0.060
PromoterAI		0.025	Neutral

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: rs781854646; hg19: chrX-153200760;