3-8623562-C-A

Variant names:

• chr3-8623562-C-A
• rs761174303
• NM_001256748.3:c.968G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001256748.3(SSUH2):​c.968G>T​(p.Arg323Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000215 in 1,396,676 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SSUH2 NM_001256748.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.48

Genes affected

SSUH2 (HGNC:24809): (ssu-2 homolog) Involved in odontogenesis. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.849

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSUH2	NM_001256748.3	c.968G>T	p.Arg323Leu	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.968G>T	p.Arg323Leu	missense_variant	Exon 11 of 12	2	NM_001256748.3	ENSP00000439378.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000128 AC: 2 AN: 155678 Hom.: 0 AF XY: 0.0000244 AC XY: 2 AN XY: 81980

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 SAS exome AF: 0.0000879

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1396676 Hom.: 0 Cov.: 29 AF XY: 0.00000435 AC XY: 3 AN XY: 689004

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000379

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	.;T;T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.84	T;.;T
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.85	D;D;D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.6	.;M;M
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-5.7	D;D;D
REVEL	Uncertain	0.47
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.66
MutPred		0.67		.;Loss of catalytic residue at R301 (P = 0.0353);Loss of catalytic residue at R301 (P = 0.0353);
MVP		0.60
MPC		0.36
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.83
gMVP		0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs761174303; hg19: chr3-8665248;