rs11553436

Positions:

• chr22-42512119-G-A
• chr22-42512119-G-C
• chr22-42512119-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015703.5(RRP7A):​c.*791C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0837 in 944,668 control chromosomes in the GnomAD database, including 5,347 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 0.12 (1221 hom., cov: 32)
  • Exomes 𝑓: 0.078 (4126 hom.)
• Consequence: RRP7A NM_015703.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.749

Genes affected

RRP7A (HGNC:24286): (ribosomal RNA processing 7 homolog A) Enables RNA binding activity. Predicted to be involved in rRNA processing and ribosomal small subunit assembly. Predicted to act upstream of or within blastocyst formation. Predicted to be located in nucleoplasm. Predicted to be part of CURI complex and UTP-C complex. Implicated in primary autosomal recessive microcephaly. [provided by Alliance of Genome Resources, Apr 2022]

SERHL (HGNC:14408): (serine hydrolase like (pseudogene)) Predicted to enable hydrolase activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRP7A	NM_015703.5	c.*791C>T		3_prime_UTR_variant	7/7	ENST00000323013.7	NP_056518.2
SERHL	NR_027786.1	n.916G>A		splice_region_variant, non_coding_transcript_exon_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRP7A	ENST00000323013.7	c.*791C>T		3_prime_UTR_variant	7/7	1	NM_015703.5	ENSP00000321449	P1
SERHL	ENST00000359906.7	n.942G>A		splice_region_variant, non_coding_transcript_exon_variant	11/11	1
SERHL	ENST00000642172.1	n.712G>A		splice_region_variant, non_coding_transcript_exon_variant	10/10

Frequencies

GnomAD3 genomes AF: 0.116 AC: 16891 AN: 145650 Hom.: 1218 Cov.: 32

Gnomad AFR AF: 0.0678

Gnomad AMI AF: 0.0376

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.00160

Gnomad SAS AF: 0.0400

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.0638

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.0778 AC: 62173 AN: 798894 Hom.: 4126 Cov.: 24 AF XY: 0.0743 AC XY: 30859 AN XY: 415176

Gnomad4 AFR exome AF: 0.0421

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.0396

Gnomad4 EAS exome AF: 0.000518

Gnomad4 SAS exome AF: 0.0316

Gnomad4 FIN exome AF: 0.140

Gnomad4 NFE exome AF: 0.0834

Gnomad4 OTH exome AF: 0.0874

GnomAD4 genome AF: 0.116 AC: 16899 AN: 145774 Hom.: 1221 Cov.: 32 AF XY: 0.116 AC XY: 8241 AN XY: 70966

Gnomad4 AFR AF: 0.0677

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.0608

Gnomad4 EAS AF: 0.00161

Gnomad4 SAS AF: 0.0402

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.0994

Alfa AF: 0.0657 Hom.: 84

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.0
DANN	Benign	0.81

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: rs11553436; hg19: chr22-42908125;