3-8629678-G-T

Variant names:

• chr3-8629678-G-T
• NM_001256748.3:c.574C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001256748.3(SSUH2):​c.574C>A​(p.His192Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000282 in 1,063,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: SSUH2 NM_001256748.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.37

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39398408).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSUH2	NM_001256748.3	c.574C>A	p.His192Asn	missense_variant	Exon 7 of 12	ENST00000544814.7	NP_001243677.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSUH2	ENST00000544814.7	c.574C>A	p.His192Asn	missense_variant	Exon 7 of 12	2	NM_001256748.3	ENSP00000439378.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000282 AC: 3 AN: 1063260 Hom.: 0 Cov.: 32 AF XY: 0.00000187 AC XY: 1 AN XY: 533760

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000386

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.508C>A (p.H170N) alteration is located in exon 7 (coding exon 4) of the SSUH2 gene. This alteration results from a C to A substitution at nucleotide position 508, causing the histidine (H) at amino acid position 170 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.053	.;T;T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.72	T;.;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	2.0	.;M;M
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.6	D;D;D
REVEL	Benign	0.13
Sift	Benign	0.48	T;T;T
Sift4G	Benign	0.40	T;T;T
Polyphen		0.99	.;D;D
Vest4		0.60
MutPred		0.25		.;Gain of glycosylation at T174 (P = 0.0275);Gain of glycosylation at T174 (P = 0.0275);
MVP		0.092
MPC		0.31
ClinPred		0.97	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-8671364;