11-126204297-A-G

Variant names:

• chr11-126204297-A-G
• rs2276312
• NM_032795.3:c.828T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_032795.3(RPUSD4):​c.828T>C​(p.Ser276Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,611,554 control chromosomes in the GnomAD database, including 27,064 homozygotes. 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: 𝑓 0.14 (2644 hom., cov: 32)
  • Exomes 𝑓: 0.15 (24420 hom.)
• Consequence: RPUSD4 NM_032795.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513
• Publications: 22 publications found

Genes affected

RPUSD4 (HGNC:25898): (RNA pseudouridine synthase D4) Enables mitochondrial ribosomal large subunit rRNA binding activity; pseudouridine synthase activity; and tRNA binding activity. Involved in mitochondrial tRNA pseudouridine synthesis and positive regulation of mitochondrial translation. Located in mitochondrion; nucleoplasm; and ribonucleoprotein granule. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=-0.513 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPUSD4	NM_032795.3	c.828T>C	p.Ser276Ser	synonymous_variant	Exon 6 of 7	ENST00000298317.9	NP_116184.2
RPUSD4	NM_001363516.2	c.828T>C	p.Ser276Ser	synonymous_variant	Exon 6 of 7		NP_001350445.1
RPUSD4	NM_001144827.2	c.735T>C	p.Ser245Ser	synonymous_variant	Exon 6 of 7		NP_001138299.1
RPUSD4	XM_011543039.3	c.249T>C	p.Ser83Ser	synonymous_variant	Exon 4 of 5		XP_011541341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPUSD4	ENST00000298317.9	c.828T>C	p.Ser276Ser	synonymous_variant	Exon 6 of 7	1	NM_032795.3	ENSP00000298317.4

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21890 AN: 152072 Hom.: 2644 Cov.: 32

Gnomad AFR AF: 0.0650

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.148

GnomAD2 exomes AF: 0.214 AC: 53384 AN: 249444 AF XY: 0.209

Gnomad AFR exome AF: 0.0638

Gnomad AMR exome AF: 0.385

Gnomad ASJ exome AF: 0.185

Gnomad EAS exome AF: 0.653

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.122

Gnomad OTH exome AF: 0.191

GnomAD4 exome AF: 0.149 AC: 218130 AN: 1459364 Hom.: 24420 Cov.: 31 AF XY: 0.152 AC XY: 110267 AN XY: 726064

African (AFR) AF: 0.0589 AC: 1969 AN: 33444

American (AMR) AF: 0.372 AC: 16464 AN: 44260

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 4840 AN: 26108

East Asian (EAS) AF: 0.638 AC: 25243 AN: 39596

South Asian (SAS) AF: 0.260 AC: 22346 AN: 85986

European-Finnish (FIN) AF: 0.125 AC: 6637 AN: 53158

Middle Eastern (MID) AF: 0.156 AC: 900 AN: 5756

European-Non Finnish (NFE) AF: 0.117 AC: 129593 AN: 1110756

Other (OTH) AF: 0.168 AC: 10138 AN: 60300

GnomAD4 genome AF: 0.144 AC: 21894 AN: 152190 Hom.: 2644 Cov.: 32 AF XY: 0.154 AC XY: 11431 AN XY: 74408

African (AFR) AF: 0.0649 AC: 2695 AN: 41540

American (AMR) AF: 0.265 AC: 4040 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 644 AN: 3470

East Asian (EAS) AF: 0.644 AC: 3322 AN: 5158

South Asian (SAS) AF: 0.264 AC: 1272 AN: 4826

European-Finnish (FIN) AF: 0.126 AC: 1338 AN: 10592

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8104 AN: 68016

Other (OTH) AF: 0.148 AC: 314 AN: 2116

Alfa AF: 0.139 Hom.: 4302

Bravo AF: 0.156

Asia WGS AF: 0.426 AC: 1477 AN: 3478

EpiCase AF: 0.118

EpiControl AF: 0.125

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.5
DANN	Benign	0.68
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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: rs2276312; hg19: chr11-126074192; COSMIC: COSV100028610; COSMIC: COSV100028610;