Genetic Variant SSUH2:p.Pro24Leu (chr3-8635815-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001256748.3(SSUH2):c.71C>T(p.Pro24Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 1,536,002 control chromosomes in the GnomAD database, including 186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 96 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 90 hom. )

Consequence

SSUH2
NM_001256748.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.18

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=0.0075953305).

BP6

Variant 3-8635815-G-A is Benign according to our data. Variant chr3-8635815-G-A is described in ClinVar as [Benign]. Clinvar id is 784465.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSUH2	NM_001256748.3 link	c.71C>T	p.Pro24Leu	missense_variant	Exon 2 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.71C>T	p.Pro24Leu	missense_variant	Exon 2 of 12	2	NM_001256748.3	ENSP00000439378.1		Q9Y2M2-2

Frequencies

GnomAD3 genomes

AF:

0.0195

AC:

2968

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0671

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00824

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0143

GnomAD2 exomes

AF:

0.00418

AC:

577

AN:

138032

AF XY:

0.00310

show subpopulations

Gnomad AFR exome

AF:

0.0700

Gnomad AMR exome

AF:

0.00365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000286

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000395

Gnomad OTH exome

AF:

0.00239

GnomAD4 exome

AF:

0.00232

AC:

3217

AN:

1383698

Hom.:

Cov.:

AF XY:

0.00204

AC XY:

1390

AN XY:

682780

show subpopulations

African (AFR)

AF:

0.0744

AC:

2350

AN:

31578

American (AMR)

AF:

0.00440

AC:

157

AN:

35690

Ashkenazi Jewish (ASJ)

AF:

0.0000397

AC:

AN:

25182

East Asian (EAS)

AF:

0.0000840

AC:

AN:

35732

South Asian (SAS)

AF:

0.000404

AC:

AN:

79188

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33890

Middle Eastern (MID)

AF:

0.00860

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.000277

AC:

299

AN:

1078832

Other (OTH)

AF:

0.00563

AC:

326

AN:

57910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

163

325

488

650

813

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0195

AC:

2976

AN:

152304

Hom.:

Cov.:

AF XY:

0.0189

AC XY:

1405

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0671

AC:

2790

AN:

41558

American (AMR)

AF:

0.00823

AC:

126

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00104

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000353

AC:

AN:

68028

Other (OTH)

AF:

0.0142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

147

293

440

586

733

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00942

Hom.:

Bravo

AF:

0.0224

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ExAC

AF:

0.00268

AC:

Asia WGS

AF:

0.00520

AC:

AN:

3478

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

- -

Jun 26, 2018

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

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.75

T;.

MetaRNN

Benign

0.0076

T;T

MetaSVM

Benign

-0.72

PhyloP100

3.2

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-7.0

D;D

REVEL

Benign

0.29

Sift

Uncertain

0.0020

D;D

Sift4G

Pathogenic

0.0

D;D

Vest4

0.37

MVP

0.56

MPC

0.33

ClinPred

0.040

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.51

Mutation Taster

=282/18

polymorphism

(source)

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

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chr3-8635815-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