chr1-1542094-G-C

Position:

• chr1-1542094-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014188.3(SSU72):​c.557C>G​(p.Thr186Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SSU72 NM_014188.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.46

Genes affected

SSU72 (HGNC:25016): (SSU72 homolog, RNA polymerase II CTD phosphatase) Enables RNA polymerase II CTD heptapeptide repeat phosphatase activity. Involved in dephosphorylation of RNA polymerase II C-terminal domain and mRNA polyadenylation. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10270035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSU72	NM_014188.3	c.557C>G	p.Thr186Ser	missense_variant	5/5	ENST00000291386.4	NP_054907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSU72	ENST00000291386.4	c.557C>G	p.Thr186Ser	missense_variant	5/5	1	NM_014188.3	ENSP00000291386.3
SSU72	ENST00000378726.1	n.1818C>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 09, 2024

The c.557C>G (p.T186S) alteration is located in exon 5 (coding exon 5) of the SSU72 gene. This alteration results from a C to G substitution at nucleotide position 557, causing the threonine (T) at amino acid position 186 to be replaced by a serine (S). 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	0.074
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	19
DANN	Benign	0.69
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.34
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.36	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.17
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.069
MutPred		0.31		Gain of catalytic residue at T186 (P = 0.0061);
MVP		0.11
MPC		1.1
ClinPred		0.32	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.20
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-1477474;