rs769878746

Variant names:

• chr3-8627752-C-A
• rs769878746
• NM_001256748.3:c.620G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-8627752-C-A
• chr3-8627752-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4 BS2

The NM_001256748.3(SSUH2):​c.620G>T​(p.Arg207Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,457,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. R207H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SSUH2 NM_001256748.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3359801).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSUH2	NM_001256748.3	c.620G>T	p.Arg207Leu	missense_variant	Exon 8 of 12	ENST00000544814.7	NP_001243677.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSUH2	ENST00000544814.7	c.620G>T	p.Arg207Leu	missense_variant	Exon 8 of 12	2	NM_001256748.3	ENSP00000439378.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1457776 Hom.: 0 Cov.: 33 AF XY: 0.00000414 AC XY: 3 AN XY: 725224

African (AFR) AF: 0.00 AC: 0 AN: 33304

American (AMR) AF: 0.00 AC: 0 AN: 43984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26026

East Asian (EAS) AF: 0.00 AC: 0 AN: 39202

South Asian (SAS) AF: 0.0000350 AC: 3 AN: 85820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110284

Other (OTH) AF: 0.00 AC: 0 AN: 60206

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.047	.;T;T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.0096
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.76	T;.;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.3	.;M;M
PhyloP100		1.4
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.6	D;D;D
REVEL	Benign	0.12
Sift	Benign	0.66	T;T;T
Sift4G	Benign	0.65	T;T;T
Polyphen		0.011	.;B;B
Vest4		0.67
MutPred		0.36		.;Gain of glycosylation at S190 (P = 0.0168);Gain of glycosylation at S190 (P = 0.0168);
MVP		0.13
MPC		0.12
ClinPred		0.94	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.47
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs769878746; hg19: chr3-8669438;