Variant chr22-26483980-GGAGGCGGCGCCCCGGGGGAGA-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4BP6_ModerateBA1

The NM_001013694.3(SRRD):c.129_149delGAGAGAGGCGGCGCCCCGGGG(p.Arg44_Gly50del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 1,332,650 control chromosomes in the GnomAD database, including 520,703 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.83 ( 51022 hom., cov: 0)

Exomes 𝑓: 0.88 ( 469681 hom. )

Consequence

SRRD
NM_001013694.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.735

Variant links:

Genes affected

SRRD (HGNC:33910): (SRR1 domain containing) Predicted to be involved in microtubule-based process; regulation of circadian rhythm; and regulation of heme biosynthetic process. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SRRD links:

HPS4 (HGNC:15844): (HPS4 biogenesis of lysosomal organelles complex 3 subunit 2) This gene encodes a protein component of biogenesis of lysosome-related organelles complexes (BLOC). BLOC complexes are important for the formation of endosomal-lysosomal organelles such as melanosomes and platelet dense granules. Mutations in this gene result in subtype 4 of Hermansky-Pudlak syndrome, a form of albinism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

HPS4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001013694.3.

BP6

Variant 22-26483980-GGAGGCGGCGCCCCGGGGGAGA-G is Benign according to our data. Variant chr22-26483980-GGAGGCGGCGCCCCGGGGGAGA-G is described in ClinVar as [Benign]. Clinvar id is 402950.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRRD	NM_001013694.3 linkuse as main transcript	c.129_149delGAGAGAGGCGGCGCCCCGGGG	p.Arg44_Gly50del	disruptive_inframe_deletion	1/7	ENST00000215917.11	NP_001013716.2	Q9UH36
SRRD	XM_017028799.3 linkuse as main transcript	c.129_149delGAGAGAGGCGGCGCCCCGGGG	p.Arg44_Gly50del	disruptive_inframe_deletion	1/6		XP_016884288.1
SRRD	XM_011530178.3 linkuse as main transcript	c.-131_-111delGAGAGAGGCGGCGCCCCGGGG		5_prime_UTR_variant	1/7		XP_011528480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRRD	ENST00000215917.11 linkuse as main transcript	c.129_149delGAGAGAGGCGGCGCCCCGGGG	p.Arg44_Gly50del	disruptive_inframe_deletion	1/7	1	NM_001013694.3	ENSP00000215917.6		Q9UH36
HPS4	ENST00000699250.1 linkuse as main transcript	c.-668_-648delTCTCCCCCGGGGCGCCGCCTC		upstream_gene_variant				ENSP00000514237.1		A0A8V8TMY3

Frequencies

GnomAD3 genomes

AF:

0.832

AC:

120670

AN:

145092

Hom.:

51014

Cov.:

show subpopulations

Gnomad AFR

AF:

0.696

Gnomad AMI

AF:

0.820

Gnomad AMR

AF:

0.768

Gnomad ASJ

AF:

0.867

Gnomad EAS

AF:

0.869

Gnomad SAS

AF:

0.892

Gnomad FIN

AF:

0.955

Gnomad MID

AF:

0.909

Gnomad NFE

AF:

0.901

Gnomad OTH

AF:

0.841

GnomAD3 exomes

AF:

0.701

AC:

6762

AN:

9648

Hom.:

2669

AF XY:

0.704

AC XY:

4143

AN XY:

5884

show subpopulations

Gnomad AFR exome

AF:

0.398

Gnomad AMR exome

AF:

0.621

Gnomad ASJ exome

AF:

0.710

Gnomad EAS exome

AF:

0.760

Gnomad SAS exome

AF:

0.681

Gnomad FIN exome

AF:

0.803

Gnomad NFE exome

AF:

0.725

Gnomad OTH exome

AF:

0.734

GnomAD4 exome

AF:

0.877

AC:

1041942

AN:

1187452

Hom.:

469681

AF XY:

0.878

AC XY:

506057

AN XY:

576574

show subpopulations

Gnomad4 AFR exome

AF:

0.669

Gnomad4 AMR exome

AF:

0.728

Gnomad4 ASJ exome

AF:

0.836

Gnomad4 EAS exome

AF:

0.867

Gnomad4 SAS exome

AF:

0.876

Gnomad4 FIN exome

AF:

0.944

Gnomad4 NFE exome

AF:

0.884

Gnomad4 OTH exome

AF:

0.867

GnomAD4 genome

AF:

0.831

AC:

120720

AN:

145198

Hom.:

51022

Cov.:

AF XY:

0.832

AC XY:

58656

AN XY:

70508

show subpopulations

Gnomad4 AFR

AF:

0.696

Gnomad4 AMR

AF:

0.767

Gnomad4 ASJ

AF:

0.867

Gnomad4 EAS

AF:

0.869

Gnomad4 SAS

AF:

0.893

Gnomad4 FIN

AF:

0.955

Gnomad4 NFE

AF:

0.901

Gnomad4 OTH

AF:

0.838

Bravo

AF:

0.812

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over