Variant chr1-223227732-G-A 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.923C>T(p.Thr308Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,459,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SUSD4
NM_017982.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.93

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:

SUSD4 (HGNC:):

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=0.306005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUSD4	NM_017982.4 linkuse as main transcript	c.923C>T	p.Thr308Met	missense_variant	7/9	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.923C>T	p.Thr308Met	missense_variant	7/9	1	NM_017982.4	ENSP00000355843.4	Q5VX71-1
SUSD4	ENST00000608996.5 linkuse as main transcript	c.839C>T	p.Thr280Met	missense_variant	6/8	5		ENSP00000477432.1	V9GZ49
SUSD4	ENST00000484758.6 linkuse as main transcript	c.716C>T	p.Thr239Met	missense_variant	6/8	2		ENSP00000477374.1	B7Z369

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1459128

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725538

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000451

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

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

Aug 27, 2024

The c.923C>T (p.T308M) alteration is located in exon 7 (coding exon 6) of the SUSD4 gene. This alteration results from a C to T substitution at nucleotide position 923, causing the threonine (T) at amino acid position 308 to be replaced by a methionine (M). 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

0.089

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.074

T;T;.;.

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

.;D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.31

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.81

L;L;.;.

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.0

N;N;.;.

REVEL

Benign

0.21

Sift

Benign

0.071

T;T;.;.

Sift4G

Uncertain

0.0050

D;D;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.18

MutPred

0.71

Loss of disorder (P = 0.0696);Loss of disorder (P = 0.0696);.;Loss of disorder (P = 0.0696);

MVP

0.64

MPC

0.55

ClinPred

0.83

GERP RS

4.9

Varity_R

0.096

gMVP

0.43

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