9-112080094-C-G

Position:

• chr9-112080094-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022486.5(SUSD1):​c.1546G>C​(p.Asp516His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 31)
• Consequence: SUSD1 NM_022486.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36

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 (HGNC:):

ACMG classification

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=0.20218036).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUSD1	NM_022486.5	c.1546G>C	p.Asp516His	missense_variant	11/17	ENST00000374270.8	NP_071931.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUSD1	ENST00000374270.8	c.1546G>C	p.Asp516His	missense_variant	11/17	1	NM_022486.5	ENSP00000363388.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 19, 2024

The c.1546G>C (p.D516H) alteration is located in exon 11 (coding exon 11) of the SUSD1 gene. This alteration results from a G to C substitution at nucleotide position 1546, causing the aspartic acid (D) at amino acid position 516 to be replaced by a histidine (H). 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	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	.;T;.
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.46	N
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.6	.;M;M
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.0	N;N;N
REVEL	Benign	0.16
Sift	Benign	0.033	D;D;D
Sift4G	Uncertain	0.010	D;D;D
Polyphen		0.99	D;D;D
Vest4		0.30
MutPred		0.42		Gain of MoRF binding (P = 0.0751);Gain of MoRF binding (P = 0.0751);Gain of MoRF binding (P = 0.0751);
MVP		0.30
MPC		0.22
ClinPred		0.82	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-114842374;