Variant chr3-8630810-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001256748.3(SSUH2):c.520G>A(p.Val174Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000335 in 1,462,278 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. V174F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

SSUH2
NM_001256748.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.76

Variant links:

Genes affected

SSUH2 (HGNC:24809): (ssu-2 homolog) Involved in odontogenesis. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SSUH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.24212196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SSUH2	NM_001256748.3 linkuse as main transcript	c.520G>A	p.Val174Ile	missense_variant	6/12	ENST00000544814.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SSUH2	ENST00000544814.7 linkuse as main transcript	c.520G>A	p.Val174Ile	missense_variant	6/12	2	NM_001256748.3	P1	Q9Y2M2-2

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000250

AC:

AN:

159768

Hom.:

AF XY:

0.0000115

AC XY:

AN XY:

87108

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000650

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000298

AC:

AN:

1310096

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

646444

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000124

Gnomad4 ASJ exome

AF:

0.0000492

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000266

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000154

Gnomad4 OTH exome

AF:

0.0000376

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000567

ExAC

AF:

0.0000412

AC:

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 03, 2022

The c.454G>A (p.V152I) alteration is located in exon 6 (coding exon 3) of the SSUH2 gene. This alteration results from a G to A substitution at nucleotide position 454, causing the valine (V) at amino acid position 152 to be replaced by an isoleucine (I). 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

0.094

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

.;T;T

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.73

T;.;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.0

.;M;M

MutationTaster

Benign

0.80

D;D;D;D

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.47

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.21

T;T;T

Sift4G

Benign

0.28

T;T;T

Polyphen

0.95

.;P;P

Vest4

0.44

MutPred

0.49

.;Gain of catalytic residue at V152 (P = 0.0315);Gain of catalytic residue at V152 (P = 0.0315);

MVP

0.030

MPC

0.31

ClinPred

0.64

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.099

gMVP

0.24

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