Genetic Variant SRRD:p.Glu10Gly (chr22-26483919-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001013694.3(SRRD):c.29A>G(p.Glu10Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

SRRD
NM_001013694.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28

Publications

0 publications found

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 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

HPS4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1034863).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRRD	NM_001013694.3	MANE Select	c.29A>G	p.Glu10Gly	missense	Exon 1 of 7	NP_001013716.2	Q9UH36
HPS4	NM_022081.6	MANE Select	c.-724T>C		upstream_gene	N/A	NP_071364.4
HPS4	NM_001349900.2		c.-724T>C		upstream_gene	N/A	NP_001336829.1	F1LLU8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRRD	ENST00000215917.11	TSL:1 MANE Select	c.29A>G	p.Glu10Gly	missense	Exon 1 of 7	ENSP00000215917.6	Q9UH36
SRRD	ENST00000942937.1		c.29A>G	p.Glu10Gly	missense	Exon 1 of 8	ENSP00000612996.1
SRRD	ENST00000885114.1		c.29A>G	p.Glu10Gly	missense	Exon 1 of 7	ENSP00000555173.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Asia WGS

AF:

0.000289

AC:

AN:

3472

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.051

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.0086

LIST_S2

Benign

0.39

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.1

PhyloP100

1.3

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.4

REVEL

Benign

0.069

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.011

Polyphen

0.0030

Vest4

0.15

MutPred

0.15

Gain of loop (P = 0.0121)

MVP

0.33

MPC

0.027

ClinPred

0.30

GERP RS

2.6

PromoterAI

0.17

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.086

gMVP

0.38

Mutation Taster

=98/2

polymorphism

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over