Variant chr1-223223281-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_017982.4(SUSD4):c.1412C>A(p.Ala471Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000405 in 1,408,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

SUSD4
NM_017982.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.59

Variant links:

Genes affected

SUSD4 (HGNC:25470): (sushi domain containing 4) Involved in negative regulation of complement activation, alternative pathway and negative regulation of complement activation, classical pathway. Predicted to be located in extracellular region. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SUSD4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37931925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUSD4	NM_017982.4 linkuse as main transcript	c.1412C>A	p.Ala471Glu	missense_variant	8/9	ENST00000366878.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUSD4	ENST00000366878.9 linkuse as main transcript	c.1412C>A	p.Ala471Glu	missense_variant	8/9	1	NM_017982.4	P1	Q5VX71-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000488

AC:

AN:

204944

Hom.:

AF XY:

0.00

AC XY:

AN XY:

109328

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000103

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000405

AC:

AN:

1408756

Hom.:

Cov.:

AF XY:

0.0000359

AC XY:

AN XY:

695470

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000515

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 20, 2023

The c.1412C>A (p.A471E) alteration is located in exon 8 (coding exon 7) of the SUSD4 gene. This alteration results from a C to A substitution at nucleotide position 1412, causing the alanine (A) at amino acid position 471 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.034

T;T;.;.

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.83

.;T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.38

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.97

L;L;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.1

N;N;.;.

REVEL

Benign

0.15

Sift

Uncertain

0.0060

D;D;.;.

Sift4G

Uncertain

0.020

D;D;D;D

Polyphen

0.96

D;D;.;.

Vest4

0.57

MutPred

0.072

Gain of relative solvent accessibility (P = 0.0483);Gain of relative solvent accessibility (P = 0.0483);.;Gain of relative solvent accessibility (P = 0.0483);

MVP

0.29

MPC

0.58

ClinPred

0.76

GERP RS

3.9

Varity_R

0.27

gMVP

0.48

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

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