Genetic Variant ENST00000359906.8:n.947G>C (chr22-42512119-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000359906.8(SERHL):n.947G>C variant causes a splice region, non coding transcript exon change involving the alteration of a non-conserved nucleotide. 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 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SERHL
ENST00000359906.8 splice_region, non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.749

Publications

0 publications found

Variant links:

Genes affected

SERHL (HGNC:):

SERHL links:

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]

RRP7A links:

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

SERHL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRP7A	NM_015703.5 link	c.*791C>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000323013.7	NP_056518.2	Q9Y3A4
SERHL	NR_027786.1 link	n.916G>C		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 link	c.*791C>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_015703.5	ENSP00000321449.6		Q9Y3A4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

147464

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000193

AC:

161

AN:

835030

Hom.:

Cov.:

AF XY:

0.000205

AC XY:

AN XY:

433886

show subpopulations

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

African (AFR)

AF:

0.000146

AC:

AN:

20612

American (AMR)

AF:

0.0000264

AC:

AN:

37890

Ashkenazi Jewish (ASJ)

AF:

0.000324

AC:

AN:

18500

East Asian (EAS)

AF:

0.000259

AC:

AN:

27026

South Asian (SAS)

AF:

0.0000413

AC:

AN:

72642

European-Finnish (FIN)

AF:

0.0000664

AC:

AN:

45214

Middle Eastern (MID)

AF:

0.000246

AC:

AN:

4064

European-Non Finnish (NFE)

AF:

0.000225

AC:

129

AN:

572616

Other (OTH)

AF:

0.000219

AC:

AN:

36466

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.232

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

147584

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71864

African (AFR)

AF:

0.00

AC:

AN:

40308

American (AMR)

AF:

0.00

AC:

AN:

14690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3420

East Asian (EAS)

AF:

0.00

AC:

AN:

4972

South Asian (SAS)

AF:

0.00

AC:

AN:

4464

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9952

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66600

Other (OTH)

AF:

0.00

AC:

AN:

2034

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.6

(source)

DANN

Benign

0.68

PhyloP100

0.75

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over