3-8627716-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001256748.3(SSUH2):c.656C>T(p.Ala219Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000927 in 1,605,610 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A219T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0044 ( 4 hom., cov: 34)

Exomes 𝑓: 0.00056 ( 6 hom. )

Consequence

SSUH2
NM_001256748.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.08

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

dentin dysplasia type I
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SSUH2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0076256096).

BP6

Variant 3-8627716-G-A is Benign according to our data. Variant chr3-8627716-G-A is described in ClinVar as [Benign]. Clinvar id is 711878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000559 (813/1453316) while in subpopulation AFR AF = 0.0182 (604/33098). AF 95% confidence interval is 0.017. There are 6 homozygotes in GnomAdExome4. There are 342 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 676 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSUH2	NM_001256748.3 link	c.656C>T	p.Ala219Val	missense_variant	Exon 8 of 12	ENST00000544814.7	NP_001243677.1	Q9Y2M2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSUH2	ENST00000544814.7 link	c.656C>T	p.Ala219Val	missense_variant	Exon 8 of 12	2	NM_001256748.3	ENSP00000439378.1		Q9Y2M2-2

Frequencies

GnomAD3 genomes

AF:

0.00442

AC:

672

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0148

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00115

AC:

281

AN:

244772

AF XY:

0.000868

show subpopulations

Gnomad AFR exome

AF:

0.0151

Gnomad AMR exome

AF:

0.000969

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000629

Gnomad OTH exome

AF:

0.000337

GnomAD4 exome

AF:

0.000559

AC:

813

AN:

1453316

Hom.:

Cov.:

AF XY:

0.000473

AC XY:

342

AN XY:

722826

show subpopulations

African (AFR)

AF:

0.0182

AC:

604

AN:

33098

American (AMR)

AF:

0.00118

AC:

AN:

43332

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25890

East Asian (EAS)

AF:

0.000103

AC:

AN:

38774

South Asian (SAS)

AF:

0.000129

AC:

AN:

85404

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53188

Middle Eastern (MID)

AF:

0.00192

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.0000469

AC:

AN:

1107930

Other (OTH)

AF:

0.00132

AC:

AN:

59962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

127

170

212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00444

AC:

676

AN:

152294

Hom.:

Cov.:

AF XY:

0.00461

AC XY:

343

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0149

AC:

619

AN:

41560

American (AMR)

AF:

0.00255

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.000414

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68020

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

120

150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00172

Hom.:

Bravo

AF:

0.00535

ESP6500AA

AF:

0.0138

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00138

AC:

167

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000548

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0074

.;T;T

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.77

T;.;T

MetaRNN

Benign

0.0076

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;N;N

PhyloP100

3.1

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.065

Sift

Benign

0.084

T;T;T

Sift4G

Benign

0.14

T;T;T

Polyphen

0.055

.;B;B

Vest4

0.32

MVP

0.014

MPC

0.049

ClinPred

0.015

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.037

gMVP

0.28

Mutation Taster

=94/6

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

3-8627716-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over