dbSNP rs777374175: SSUH2:p.Ala219Ser (chr3-8627717-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001256748.3(SSUH2):c.655G>T(p.Ala219Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A219V) has been classified as Benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SSUH2
NM_001256748.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.28

Publications

0 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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020069033).

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.655G>T	p.Ala219Ser	missense	Exon 8 of 12	NP_001243677.1	Q9Y2M2-2
SSUH2	NM_001256749.3		c.436G>T	p.Ala146Ser	missense	Exon 8 of 12	NP_001243678.1	Q9Y2M2-3
SSUH2	NM_015931.4		c.436G>T	p.Ala146Ser	missense	Exon 8 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.655G>T	p.Ala219Ser	missense	Exon 8 of 12	ENSP00000439378.1	Q9Y2M2-2
SSUH2	ENST00000341795.7	TSL:1	c.436G>T	p.Ala146Ser	missense	Exon 8 of 12	ENSP00000339150.4	Q9Y2M2-3
SSUH2	ENST00000420394.5	TSL:1	c.436G>T	p.Ala146Ser	missense	Exon 8 of 12	ENSP00000390328.2	F8WDV4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453726

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723044

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33116

American (AMR)

AF:

0.00

AC:

AN:

43382

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25928

East Asian (EAS)

AF:

0.0000258

AC:

AN:

38806

South Asian (SAS)

AF:

0.00

AC:

AN:

85440

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53190

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108144

Other (OTH)

AF:

0.00

AC:

AN:

59984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.34

(source)

DANN

Benign

0.21

DEOGEN2

Benign

0.0010

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.58

M_CAP

Benign

0.0017

MetaRNN

Benign

0.020

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-2.8

PhyloP100

1.3

PrimateAI

Benign

0.33

PROVEAN

Benign

1.3

REVEL

Benign

0.017

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0040

Vest4

0.16

MutPred

0.30

Loss of relative solvent accessibility (P = 0.0071)

MVP

0.014

MPC

0.046

ClinPred

0.037

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.017

gMVP

0.12

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over