dbSNP rs895448539: SRRD:p.Ala47Glu (chr22-26484030-C-A) – 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.140C>A(p.Ala47Glu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A47V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SRRD
NM_001013694.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.884

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:

Genome browser will be placed here

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=0.076301605).

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.140C>A	p.Ala47Glu	missense	Exon 1 of 7	NP_001013716.2	Q9UH36
HPS4	NM_022081.6	MANE Select	c.-835G>T		upstream_gene	N/A	NP_071364.4
HPS4	NM_001349900.2		c.-835G>T		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.140C>A	p.Ala47Glu	missense	Exon 1 of 7	ENSP00000215917.6	Q9UH36
SRRD	ENST00000942937.1		c.140C>A	p.Ala47Glu	missense	Exon 1 of 8	ENSP00000612996.1
SRRD	ENST00000885114.1		c.140C>A	p.Ala47Glu	missense	Exon 1 of 7	ENSP00000555173.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

742062

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

371188

African (AFR)

AF:

0.00

AC:

AN:

18022

American (AMR)

AF:

0.00

AC:

AN:

15336

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12786

East Asian (EAS)

AF:

0.00

AC:

AN:

13902

South Asian (SAS)

AF:

0.00

AC:

AN:

49982

European-Finnish (FIN)

AF:

0.00

AC:

AN:

15022

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2090

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

585060

Other (OTH)

AF:

0.00

AC:

AN:

29862

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Benign

-0.32

CADD

Benign

9.1

(source)

DANN

Benign

0.53

DEOGEN2

Benign

0.016

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0036

LIST_S2

Benign

0.35

M_CAP

Benign

0.043

MetaRNN

Benign

0.076

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

0.88

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.37

REVEL

Benign

0.049

Sift

Benign

0.67

Sift4G

Benign

0.43

Polyphen

0.0040

Vest4

0.26

MutPred

0.19

Gain of solvent accessibility (P = 0.0411)

MVP

0.18

MPC

0.026

ClinPred

0.12

GERP RS

0.47

PromoterAI

-0.083

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.050

gMVP

0.14

Mutation Taster

=96/4

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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