Genetic Variant NM_001256748.3:c.520G>A (chr3-8630810-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

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

Publications

2 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.24212196).

BS2

High AC in GnomAd4 at 10 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256748.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SSUH2	NM_001256748.3	MANE Select	c.520G>A	p.Val174Ile	missense	Exon 6 of 12	NP_001243677.1	Q9Y2M2-2
SSUH2	NM_001256749.3		c.301G>A	p.Val101Ile	missense	Exon 6 of 12	NP_001243678.1	Q9Y2M2-3
SSUH2	NM_015931.4		c.301G>A	p.Val101Ile	missense	Exon 6 of 12	NP_057015.2	Q9Y2M2-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SSUH2	ENST00000544814.7	TSL:2 MANE Select	c.520G>A	p.Val174Ile	missense	Exon 6 of 12	ENSP00000439378.1	Q9Y2M2-2
SSUH2	ENST00000341795.7	TSL:1	c.301G>A	p.Val101Ile	missense	Exon 6 of 12	ENSP00000339150.4	Q9Y2M2-3
SSUH2	ENST00000420394.5	TSL:1	c.301G>A	p.Val101Ile	missense	Exon 6 of 12	ENSP00000390328.2	F8WDV4

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

GnomAD2 exomes

AF:

0.0000250

AC:

AN:

159768

AF XY:

0.0000115

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 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

African (AFR)

AF:

0.00

AC:

AN:

27096

American (AMR)

AF:

0.000124

AC:

AN:

24190

Ashkenazi Jewish (ASJ)

AF:

0.0000492

AC:

AN:

20342

East Asian (EAS)

AF:

0.00

AC:

AN:

32382

South Asian (SAS)

AF:

0.000266

AC:

AN:

60262

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49670

Middle Eastern (MID)

AF:

0.000192

AC:

AN:

5212

European-Non Finnish (NFE)

AF:

0.0000154

AC:

AN:

1037724

Other (OTH)

AF:

0.0000376

AC:

AN:

53218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41438

American (AMR)

AF:

0.000327

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000412

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.73

M_CAP

Benign

0.014

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.0

PhyloP100

4.8

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.47

REVEL

Benign

0.12

Sift

Benign

0.21

Sift4G

Benign

0.28

Polyphen

0.95

Vest4

0.44

MutPred

0.49

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

Mutation Taster

=91/9

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over