9-112078565-C-A

Variant names:

• chr9-112078565-C-A
• NM_022486.5:c.1726G>T

Variant summary

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

The NM_022486.5(SUSD1):​c.1726G>T​(p.Val576Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 6.8e-7 (0 hom.)
• Consequence: SUSD1 NM_022486.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0560

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]

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=0.110925496).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUSD1	NM_022486.5	c.1726G>T	p.Val576Phe	missense_variant	Exon 12 of 17	ENST00000374270.8	NP_071931.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUSD1	ENST00000374270.8	c.1726G>T	p.Val576Phe	missense_variant	Exon 12 of 17	1	NM_022486.5	ENSP00000363388.4
SUSD1	ENST00000374264.6	c.1726G>T	p.Val576Phe	missense_variant	Exon 12 of 18	1		ENSP00000363382.2
SUSD1	ENST00000374263.7	c.1726G>T	p.Val576Phe	missense_variant	Exon 12 of 16	2		ENSP00000363381.3
SUSD1	ENST00000355396.7	c.1675G>T	p.Val559Phe	missense_variant	Exon 12 of 16	2		ENSP00000347558.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460736 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726514

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: 0.0000187

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 05, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1726G>T (p.V576F) alteration is located in exon 12 (coding exon 12) of the SUSD1 gene. This alteration results from a G to T substitution at nucleotide position 1726, causing the valine (V) at amino acid position 576 to be replaced by a phenylalanine (F). 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	0.12
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.058	.;T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.85	T;D;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	.;M;M
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Benign	0.14
Sift	Uncertain	0.015	D;D;D
Sift4G	Uncertain	0.048	D;T;D
Polyphen		0.77	P;P;P
Vest4		0.34
MutPred		0.30		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.26
MPC		0.41
ClinPred		0.83	D
GERP RS		-0.77
Varity_R		0.084
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-114840845;