chr3-33152848-A-G

Position:

• chr3-33152848-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015551.2(SUSD5):​c.1784T>C​(p.Val595Ala) 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. 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: 32)
• Consequence: SUSD5 NM_015551.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.10

Genes affected

SUSD5 (HGNC:29061): (sushi domain containing 5) Predicted to enable hyaluronic acid binding activity. Predicted to be involved in Notch signaling pathway. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.29160753).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUSD5	NM_015551.2	c.1784T>C	p.Val595Ala	missense_variant	5/5	ENST00000309558.8	NP_056366.1
SUSD5	XM_005265034.4	c.1595T>C	p.Val532Ala	missense_variant	4/4		XP_005265091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUSD5	ENST00000309558.8	c.1784T>C	p.Val595Ala	missense_variant	5/5	1	NM_015551.2	ENSP00000308727.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Oct 29, 2021

The c.1784T>C (p.V595A) alteration is located in exon 5 (coding exon 5) of the SUSD5 gene. This alteration results from a T to C substitution at nucleotide position 1784, causing the valine (V) at amino acid position 595 to be replaced by an alanine (A). 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	0.13
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.11
Sift	Benign	0.11	T
Sift4G	Benign	0.29	T
Polyphen		0.99	D
Vest4		0.31
MutPred		0.26		Loss of sheet (P = 0.0104);
MVP		0.44
MPC		0.073
ClinPred		0.70	D
GERP RS		4.6
Varity_R		0.051
gMVP		0.74

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

Other links and lift over

dbSNP: rs1575524898; hg19: chr3-33194340;