3-8623568-C-A

Variant names:

• chr3-8623568-C-A
• rs149593163
• NM_001256748.3:c.962G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001256748.3(SSUH2):​c.962G>T​(p.Arg321Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. R321H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: SSUH2 NM_001256748.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.507
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16767299).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSUH2	NM_001256748.3	c.962G>T	p.Arg321Leu	missense_variant	Exon 11 of 12	ENST00000544814.7	NP_001243677.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSUH2	ENST00000544814.7	c.962G>T	p.Arg321Leu	missense_variant	Exon 11 of 12	2	NM_001256748.3	ENSP00000439378.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398018 Hom.: 0 Cov.: 29 AF XY: 0.00000145 AC XY: 1 AN XY: 689566

African (AFR) AF: 0.00 AC: 0 AN: 31572

American (AMR) AF: 0.00 AC: 0 AN: 35672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25166

East Asian (EAS) AF: 0.00 AC: 0 AN: 35728

South Asian (SAS) AF: 0.00 AC: 0 AN: 79176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5660

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077936

Other (OTH) AF: 0.00 AC: 0 AN: 57968

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.054	.;T;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.75	T;.;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;L;L
PhyloP100		0.51
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Benign	0.074
Sift	Benign	0.079	T;T;T
Sift4G	Benign	0.30	T;T;T
Polyphen		0.83	.;P;P
Vest4		0.33
MutPred		0.43		.;Loss of disorder (P = 0.0371);Loss of disorder (P = 0.0371);
MVP		0.34
MPC		0.13
ClinPred		0.76	D
GERP RS		2.4
Varity_R		0.11
gMVP		0.50
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs149593163; hg19: chr3-8665254;