chr2-169805534-G-C

Position:

• chr2-169805534-G-C

Variant summary

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

The NM_003142.5(SSB):​c.127G>C​(p.Asp43His) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SSB NM_003142.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 10.0

Genes affected

SSB (HGNC:11316): (small RNA binding exonuclease protection factor La) The protein encoded by this gene is involved in diverse aspects of RNA metabolism, including binding and protecting poly(U) termini of nascent RNA polymerase III transcripts from exonuclease digestion, processing 5' and 3' ends of pre-tRNA precursors, acting as an RNA chaperone, and binding viral RNAs associated with hepatitis C virus. Autoantibodies reacting with this protein are found in the sera of patients with Sjogren syndrome and systemic lupus erythematosus. Alternative promoter usage results in two different transcript variants which encode the same protein. [provided by RefSeq, Jun 2014]

SSB (HGNC:):

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, 0.841

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSB	NM_003142.5	c.127G>C	p.Asp43His	missense_variant	3/12	ENST00000260956.9	NP_003133.1
SSB	NM_001294145.2	c.127G>C	p.Asp43His	missense_variant	3/12		NP_001281074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSB	ENST00000260956.9	c.127G>C	p.Asp43His	missense_variant	3/12	1	NM_003142.5	ENSP00000260956.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jan 31, 2024

The c.127G>C (p.D43H) alteration is located in exon 3 (coding exon 2) of the SSB gene. This alteration results from a G to C substitution at nucleotide position 127, causing the aspartic acid (D) at amino acid position 43 to be replaced by a histidine (H). 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	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	.;T;T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.97	D;.;D
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.5	.;M;M
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-6.1	D;D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.029	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.83, 0.83
MutPred		0.70		Loss of catalytic residue at D43 (P = 0.0151);Loss of catalytic residue at D43 (P = 0.0151);Loss of catalytic residue at D43 (P = 0.0151);
MVP		0.66
MPC		1.1
ClinPred		1.0	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.91
gMVP		0.69

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: chr2-170662044;