22-26484040-C-T

Variant names:

• chr22-26484040-C-T
• rs371251054
• NM_001013694.3:c.150C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001013694.3(SRRD):​c.150C>T​(p.Gly50Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00478 in 1,336,880 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0050 (31 hom.)
• Consequence: SRRD NM_001013694.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.643
• Publications: 0 publications found

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]

HPS4 Gene-Disease associations (from GenCC):

• Hermansky-Pudlak syndrome 4

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Ambry Genetics
• Hermansky-Pudlak syndrome with pulmonary fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 22-26484040-C-T is Benign according to our data. Variant chr22-26484040-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3238993.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.643 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 31 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013694.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRRD	NM_001013694.3	MANE Select	c.150C>T	p.Gly50Gly	synonymous	Exon 1 of 7	NP_001013716.2	Q9UH36
	HPS4	NM_001349901.1		c.-754G>A		upstream_gene	N/A	NP_001336830.1	F1LLU8
	HPS4	NM_001349896.1		c.-754G>A		upstream_gene	N/A	NP_001336825.1	Q9NQG7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRRD	ENST00000215917.11	TSL:1 MANE Select	c.150C>T	p.Gly50Gly	synonymous	Exon 1 of 7	ENSP00000215917.6	Q9UH36
	SRRD	ENST00000942937.1		c.150C>T	p.Gly50Gly	synonymous	Exon 1 of 8	ENSP00000612996.1
	SRRD	ENST00000885114.1		c.150C>T	p.Gly50Gly	synonymous	Exon 1 of 7	ENSP00000555173.1

Frequencies

GnomAD3 genomes AF: 0.00307 AC: 422 AN: 137292 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00279

Gnomad ASJ AF: 0.00546

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00230

Gnomad FIN AF: 0.000236

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00483

Gnomad OTH AF: 0.00158

GnomAD2 exomes AF: 0.00484 AC: 364 AN: 75232 AF XY: 0.00482

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00213

Gnomad ASJ exome AF: 0.0269

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000445

Gnomad NFE exome AF: 0.00480

Gnomad OTH exome AF: 0.00325

GnomAD4 exome AF: 0.00497 AC: 5967 AN: 1199456 Hom.: 31 Cov.: 35 AF XY: 0.00494 AC XY: 2922 AN XY: 591126

African (AFR) AF: 0.000959 AC: 23 AN: 23994

American (AMR) AF: 0.00233 AC: 53 AN: 22716

Ashkenazi Jewish (ASJ) AF: 0.0171 AC: 315 AN: 18450

East Asian (EAS) AF: 0.0000497 AC: 1 AN: 20124

South Asian (SAS) AF: 0.00115 AC: 80 AN: 69868

European-Finnish (FIN) AF: 0.000636 AC: 13 AN: 20452

Middle Eastern (MID) AF: 0.00527 AC: 18 AN: 3418

European-Non Finnish (NFE) AF: 0.00539 AC: 5245 AN: 973854

Other (OTH) AF: 0.00470 AC: 219 AN: 46580

GnomAD4 genome AF: 0.00307 AC: 422 AN: 137424 Hom.: 0 Cov.: 31 AF XY: 0.00272 AC XY: 181 AN XY: 66506

African (AFR) AF: 0.00125 AC: 47 AN: 37670

American (AMR) AF: 0.00278 AC: 39 AN: 14004

Ashkenazi Jewish (ASJ) AF: 0.00546 AC: 18 AN: 3296

East Asian (EAS) AF: 0.00 AC: 0 AN: 4180

South Asian (SAS) AF: 0.00230 AC: 9 AN: 3912

European-Finnish (FIN) AF: 0.000236 AC: 2 AN: 8490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 250

European-Non Finnish (NFE) AF: 0.00483 AC: 304 AN: 62900

Other (OTH) AF: 0.00156 AC: 3 AN: 1926

Alfa AF: 0.00452 Hom.: 2

Bravo AF: 0.00340

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	5.5
DANN	Benign	0.84
PhyloP100		-0.64
PromoterAI		-0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=100/0	polymorphism

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: rs371251054; hg19: chr22-26880006;