Variant chr1-223223620-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017982.4(SUSD4):c.1073G>A(p.Arg358Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000771 in 1,452,690 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R358W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

SUSD4
NM_017982.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.63

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06456682).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUSD4	NM_017982.4 linkuse as main transcript	c.1073G>A	p.Arg358Gln	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.1073G>A	p.Arg358Gln	missense_variant	8/9	1	NM_017982.4	P1	Q5VX71-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000254

AC:

AN:

235774

Hom.:

AF XY:

0.0000312

AC XY:

AN XY:

128318

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000566

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000477

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000771

AC:

112

AN:

1452690

Hom.:

Cov.:

AF XY:

0.0000776

AC XY:

AN XY:

721292

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000976

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000330

AC:

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

Jan 18, 2022

The c.1073G>A (p.R358Q) alteration is located in exon 8 (coding exon 7) of the SUSD4 gene. This alteration results from a G to A substitution at nucleotide position 1073, causing the arginine (R) at amino acid position 358 to be replaced by a glutamine (Q). 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

-0.31

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.37

DEOGEN2

Benign

0.016

T;T;.;.

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.73

.;T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.065

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.20

N;N;.;.

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

0.94

N;N;.;.

REVEL

Benign

0.079

Sift

Benign

0.92

T;T;.;.

Sift4G

Benign

0.54

T;T;T;T

Polyphen

0.040

B;B;.;.

Vest4

0.17

MutPred

0.23

Loss of glycosylation at P357 (P = 0.0737);Loss of glycosylation at P357 (P = 0.0737);.;Loss of glycosylation at P357 (P = 0.0737);

MVP

0.16

MPC

0.21

ClinPred

0.082

GERP RS

5.0

Varity_R

0.029

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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