NM_001256748.3:c.577G>C

Variant names:

• chr3-8629675-C-G
• rs144988627
• NM_001256748.3:c.577G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001256748.3(SSUH2):​c.577G>C​(p.Gly193Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000194 in 1,033,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: SSUH2 NM_001256748.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.67
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.771

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSUH2	NM_001256748.3	MANE Select	c.577G>C	p.Gly193Arg	missense	Exon 7 of 12	NP_001243677.1	Q9Y2M2-2
	SSUH2	NM_001256749.3		c.358G>C	p.Gly120Arg	missense	Exon 7 of 12	NP_001243678.1	Q9Y2M2-3
	SSUH2	NM_015931.4		c.358G>C	p.Gly120Arg	missense	Exon 7 of 12	NP_057015.2	Q9Y2M2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSUH2	ENST00000544814.7	TSL:2 MANE Select	c.577G>C	p.Gly193Arg	missense	Exon 7 of 12	ENSP00000439378.1	Q9Y2M2-2
	SSUH2	ENST00000341795.7	TSL:1	c.358G>C	p.Gly120Arg	missense	Exon 7 of 12	ENSP00000339150.4	Q9Y2M2-3
	SSUH2	ENST00000420394.5	TSL:1	c.358G>C	p.Gly120Arg	missense	Exon 7 of 12	ENSP00000390328.2	F8WDV4

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.00000194 AC: 2 AN: 1033276 Hom.: 0 Cov.: 32 AF XY: 0.00000193 AC XY: 1 AN XY: 519068

African (AFR) AF: 0.00 AC: 0 AN: 31982

American (AMR) AF: 0.00 AC: 0 AN: 37374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17986

East Asian (EAS) AF: 0.00 AC: 0 AN: 31642

South Asian (SAS) AF: 0.00 AC: 0 AN: 68620

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43242

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4228

European-Non Finnish (NFE) AF: 0.00000265 AC: 2 AN: 753808

Other (OTH) AF: 0.00 AC: 0 AN: 44394

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.036	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.52	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		4.7
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Benign	0.29
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.039	D
Polyphen		1.0	D
Vest4		0.63
MutPred		0.50		Gain of solvent accessibility (P = 6e-04)
MVP		0.38
MPC		0.35
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.69
gMVP		0.74
Mutation Taster		=86/14	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: rs144988627; hg19: chr3-8671361; COSMIC: COSV58030380; COSMIC: COSV58030380;