3-8630810-C-G

Variant names:

• chr3-8630810-C-G
• rs757266021
• NM_001256748.3:c.520G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001256748.3(SSUH2):​c.520G>C​(p.Val174Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000458 in 1,310,098 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V174F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: SSUH2 NM_001256748.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.76
• Publications: 2 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 -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 AD gene.

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.520G>C	p.Val174Leu	missense	Exon 6 of 12	NP_001243677.1	Q9Y2M2-2
	SSUH2	NM_001256749.3		c.301G>C	p.Val101Leu	missense	Exon 6 of 12	NP_001243678.1	Q9Y2M2-3
	SSUH2	NM_015931.4		c.301G>C	p.Val101Leu	missense	Exon 6 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.520G>C	p.Val174Leu	missense	Exon 6 of 12	ENSP00000439378.1	Q9Y2M2-2
	SSUH2	ENST00000341795.7	TSL:1	c.301G>C	p.Val101Leu	missense	Exon 6 of 12	ENSP00000339150.4	Q9Y2M2-3
	SSUH2	ENST00000420394.5	TSL:1	c.301G>C	p.Val101Leu	missense	Exon 6 of 12	ENSP00000390328.2	F8WDV4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000626 AC: 1 AN: 159768 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000124

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000458 AC: 6 AN: 1310098 Hom.: 0 Cov.: 30 AF XY: 0.00000464 AC XY: 3 AN XY: 646446

African (AFR) AF: 0.00 AC: 0 AN: 27096

American (AMR) AF: 0.00 AC: 0 AN: 24190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20342

East Asian (EAS) AF: 0.00 AC: 0 AN: 32382

South Asian (SAS) AF: 0.00 AC: 0 AN: 60262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49670

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5212

European-Non Finnish (NFE) AF: 0.00000578 AC: 6 AN: 1037726

Other (OTH) AF: 0.00 AC: 0 AN: 53218

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.039	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.60	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		4.8
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.18
Sift	Benign	0.094	T
Sift4G	Uncertain	0.015	D
Polyphen		0.98	D
Vest4		0.55
MutPred		0.53		Loss of methylation at K153 (P = 0.0339)
MVP		0.14
MPC		0.33
ClinPred		0.91	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.51
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs757266021; hg19: chr3-8672496;