NM_145006.4:c.139C>T

Variant names:

• chr9-93075834-C-T
• rs531952596
• NM_145006.4:c.139C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145006.4(SUSD3):​c.139C>T​(p.Arg47Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000999 in 1,601,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R47H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: SUSD3 NM_145006.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.66
• Publications: 0 publications found

Genes affected

SUSD3 (HGNC:28391): (sushi domain containing 3) Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2605709).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145006.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUSD3	NM_145006.4	MANE Select	c.139C>T	p.Arg47Cys	missense	Exon 2 of 5	NP_659443.1	Q96L08-1
	SUSD3	NM_001287005.2		c.100C>T	p.Arg34Cys	missense	Exon 3 of 6	NP_001273934.1	Q96L08-2
	SUSD3	NM_001287006.2		c.139C>T	p.Arg47Cys	missense	Exon 2 of 4	NP_001273935.1	A0A087WVN2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUSD3	ENST00000375472.8	TSL:1 MANE Select	c.139C>T	p.Arg47Cys	missense	Exon 2 of 5	ENSP00000364621.3	Q96L08-1
	SUSD3	ENST00000375469.5	TSL:5	c.100C>T	p.Arg34Cys	missense	Exon 2 of 5	ENSP00000364618.1	Q96L08-2
	SUSD3	ENST00000617293.4	TSL:3	c.139C>T	p.Arg47Cys	missense	Exon 2 of 4	ENSP00000479555.1	A0A087WVN2

Frequencies

GnomAD3 genomes AF: 0.00000669 AC: 1 AN: 149392 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 251004 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1451904 Hom.: 0 Cov.: 34 AF XY: 0.0000111 AC XY: 8 AN XY: 722252

African (AFR) AF: 0.0000301 AC: 1 AN: 33192

American (AMR) AF: 0.00 AC: 0 AN: 44392

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25752

East Asian (EAS) AF: 0.00 AC: 0 AN: 38958

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00000905 AC: 10 AN: 1105480

Other (OTH) AF: 0.0000168 AC: 1 AN: 59666

GnomAD4 genome AF: 0.00000669 AC: 1 AN: 149512 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 72784

African (AFR) AF: 0.00 AC: 0 AN: 40828

American (AMR) AF: 0.00 AC: 0 AN: 14632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5002

South Asian (SAS) AF: 0.000213 AC: 1 AN: 4698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9982

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67628

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.76	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.7
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.036
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.36	B
Vest4		0.44
MutPred		0.36		Loss of MoRF binding (P = 0.0174)
MVP		0.32
MPC		1.4
ClinPred		0.92	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.18
gMVP		0.43
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs531952596; hg19: chr9-95838116; COSMIC: COSV100968861; COSMIC: COSV100968861;