NM_001256748.3:c.619C>A

Variant names:

• chr3-8627753-G-T
• rs374521608
• NM_001256748.3:c.619C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001256748.3(SSUH2):​c.619C>A​(p.Arg207Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: SSUH2 NM_001256748.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.95
• Publications: 1 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31622142).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSUH2	NM_001256748.3	c.619C>A	p.Arg207Ser	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.619C>A	p.Arg207Ser	missense_variant	Exon 8 of 12	2	NM_001256748.3	ENSP00000439378.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0051	.;T;T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.057
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.62	T;.;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	.;M;M
PhyloP100		3.0
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.5	D;D;D
REVEL	Benign	0.048
Sift	Benign	0.45	T;T;T
Sift4G	Benign	0.51	T;T;T
Polyphen		0.056	.;B;B
Vest4		0.66
MutPred		0.31		.;Gain of glycosylation at S190 (P = 0.0168);Gain of glycosylation at S190 (P = 0.0168);
MVP		0.061
MPC		0.097
ClinPred		0.77	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.49
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs374521608; hg19: chr3-8669439;