Variant chr9-112078586-G-C 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_022486.5(SUSD1):c.1705C>G(p.Leu569Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,634 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 (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SUSD1
NM_022486.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.575

Variant links:

Genes affected

SUSD1 (HGNC:25413): (sushi domain containing 1) Predicted to enable calcium ion binding activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SUSD1 links:

SUSD1 (HGNC:):

SUSD1 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=0.041777074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUSD1	NM_022486.5 linkuse as main transcript	c.1705C>G	p.Leu569Val	missense_variant	12/17	ENST00000374270.8	NP_071931.2	Q6UWL2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SUSD1	ENST00000374270.8 linkuse as main transcript	c.1705C>G	p.Leu569Val	missense_variant	12/17	1	NM_022486.5	ENSP00000363388.4	Q6UWL2-1
SUSD1	ENST00000374264.6 linkuse as main transcript	c.1705C>G	p.Leu569Val	missense_variant	12/18	1		ENSP00000363382.2	Q6UWL2-2
SUSD1	ENST00000374263.7 linkuse as main transcript	c.1705C>G	p.Leu569Val	missense_variant	12/16	2		ENSP00000363381.3	F8WAQ1
SUSD1	ENST00000355396.7 linkuse as main transcript	c.1654C>G	p.Leu552Val	missense_variant	12/16	2		ENSP00000347558.3	H3BLV4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461634

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727094

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

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

Jun 10, 2022

The c.1705C>G (p.L569V) alteration is located in exon 12 (coding exon 12) of the SUSD1 gene. This alteration results from a C to G substitution at nucleotide position 1705, causing the leucine (L) at amino acid position 569 to be replaced by a valine (V). 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

0.10

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

7.0

DANN

Benign

0.75

DEOGEN2

Benign

0.019

.;T;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.85

T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.042

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

2.0

.;M;M

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.77

N;N;N

REVEL

Benign

0.070

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.94

T;T;T

Polyphen

0.57

P;B;P

Vest4

0.043

MutPred

0.19

Loss of stability (P = 0.1157);Loss of stability (P = 0.1157);Loss of stability (P = 0.1157);

MVP

0.21

MPC

0.48

ClinPred

0.16

GERP RS

-2.3

Varity_R

0.025

gMVP

0.34

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