Variant chr1-223223330-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017982.4(SUSD4):c.1363C>T(p.Pro455Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,458,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

SUSD4
NM_017982.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2274459).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUSD4	NM_017982.4 linkuse as main transcript	c.1363C>T	p.Pro455Ser	missense_variant	8/9	ENST00000366878.9	NP_060452.3	Q5VX71-1B3KTY0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SUSD4	ENST00000366878.9 linkuse as main transcript	c.1363C>T	p.Pro455Ser	missense_variant	8/9	1	NM_017982.4	ENSP00000355843.4	Q5VX71-1
SUSD4	ENST00000608996.5 linkuse as main transcript	c.1279C>T	p.Pro427Ser	missense_variant	7/8	5		ENSP00000477432.1	V9GZ49
SUSD4	ENST00000484758.6 linkuse as main transcript	c.1156C>T	p.Pro386Ser	missense_variant	7/8	2		ENSP00000477374.1	B7Z369

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1458012

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

725108

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:

0.0000198

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Jun 26, 2024

The c.1363C>T (p.P455S) alteration is located in exon 8 (coding exon 7) of the SUSD4 gene. This alteration results from a C to T substitution at nucleotide position 1363, causing the proline (P) at amino acid position 455 to be replaced by a serine (S). 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

0.071

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.021

T;T;.;.

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.72

.;T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.23

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.46

N;N;.;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.2

N;N;.;.

REVEL

Benign

0.15

Sift

Benign

0.13

T;T;.;.

Sift4G

Benign

0.20

T;T;T;T

Polyphen

0.78

P;P;.;.

Vest4

0.28

MutPred

0.065

Gain of phosphorylation at P455 (P = 0.0293);Gain of phosphorylation at P455 (P = 0.0293);.;Gain of phosphorylation at P455 (P = 0.0293);

MVP

0.29

MPC

0.46

ClinPred

0.63

GERP RS

5.2

Varity_R

0.075

gMVP

0.40

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