rs11553436

Variant names:

• chr22-42512119-G-A
• rs11553436
• ENST00000359906.8:n.947G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000359906.8(SERHL):​n.947G>A variant causes a splice region, non coding transcript exon 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. 1/1 splice prediction tools predict no significant impact on normal splicing. 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: SERHL ENST00000359906.8 splice_region, non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.749
• Publications: 5 publications found

Genes affected

SERHL (HGNC:):

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RRP7A	NM_015703.5	c.*791C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000323013.7	NP_056518.2
SERHL	NR_027786.1	n.916G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 11 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRP7A	ENST00000323013.7	c.*791C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_015703.5	ENSP00000321449.6

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0421 AC: 854 AN: 20262

American (AMR) AF: 0.100 AC: 3680 AN: 36760

Ashkenazi Jewish (ASJ) AF: 0.0396 AC: 723 AN: 18254

East Asian (EAS) AF: 0.000518 AC: 14 AN: 27046

South Asian (SAS) AF: 0.0316 AC: 2172 AN: 68720

European-Finnish (FIN) AF: 0.140 AC: 5838 AN: 41806

Middle Eastern (MID) AF: 0.0462 AC: 182 AN: 3940

European-Non Finnish (NFE) AF: 0.0834 AC: 45628 AN: 546834

Other (OTH) AF: 0.0874 AC: 3082 AN: 35272

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.0677 AC: 2706 AN: 39986

American (AMR) AF: 0.177 AC: 2561 AN: 14506

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 207 AN: 3406

East Asian (EAS) AF: 0.00161 AC: 8 AN: 4972

South Asian (SAS) AF: 0.0402 AC: 178 AN: 4432

European-Finnish (FIN) AF: 0.198 AC: 1925 AN: 9730

Middle Eastern (MID) AF: 0.0612 AC: 17 AN: 278

European-Non Finnish (NFE) AF: 0.138 AC: 9065 AN: 65600

Other (OTH) AF: 0.0994 AC: 200 AN: 2012

Alfa AF: 0.0346 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
PhyloP100		0.75
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: rs11553436; hg19: chr22-42908125;