22-26483980-GGAGGCGGCGCCCCGGGGGAGA-G

Position:

• chr22-26483980-GGAGGCGGCGCCCCGGGGGAGA-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BA1

The NM_001013694.3(SRRD):​c.129_149del​(p.Arg44_Gly50del) variant causes a 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 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.735

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]

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]

ACMG classification

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	UniProt
SRRD	NM_001013694.3	c.129_149del	p.Arg44_Gly50del	inframe_deletion	1/7	ENST00000215917.11
SRRD	XM_017028799.3	c.129_149del	p.Arg44_Gly50del	inframe_deletion	1/6
SRRD	XM_011530178.3	c.-131_-111del		5_prime_UTR_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRRD	ENST00000215917.11	c.129_149del	p.Arg44_Gly50del	inframe_deletion	1/7	1	NM_001013694.3	P1
HPS4	ENST00000699250.1			upstream_gene_variant				A2

Frequencies

GnomAD3 genomes AF: 0.832 AC: 120670 AN: 145092 Hom.: 51014 Cov.: 0

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

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

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.: 0 AF XY: 0.832 AC XY: 58656 AN XY: 70508

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

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs66831137; hg19: chr22-26879946;