2-169811299-G-C

Position:

chr2-169811299-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003142.5(SSB):c.1114G>C(p.Glu372Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000889 in 1,597,504 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000092 ( 0 hom. )

Consequence

SSB
NM_003142.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00

Variant links:

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 links:

METTL5 (HGNC:25006): (methyltransferase 5, N6-adenosine) Enables S-adenosyl-L-methionine binding activity and rRNA (adenine-N6-)-methyltransferase activity. Involved in positive regulation of translation and rRNA methylation. Located in nucleus; postsynapse; and presynapse. Implicated in autosomal recessive intellectual developmental disorder-72. [provided by Alliance of Genome Resources, Apr 2022]

METTL5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014285862).

BS2

High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSB	NM_003142.5 linkuse as main transcript	c.1114G>C	p.Glu372Gln	missense_variant	11/12	ENST00000260956.9	NP_003133.1	P05455
SSB	NM_001294145.2 linkuse as main transcript	c.1114G>C	p.Glu372Gln	missense_variant	11/12		NP_001281074.1	P05455

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SSB	ENST00000260956.9 linkuse as main transcript	c.1114G>C	p.Glu372Gln	missense_variant	11/12	1	NM_003142.5	ENSP00000260956.4	P05455
SSB	ENST00000409333.1 linkuse as main transcript	c.1114G>C	p.Glu372Gln	missense_variant	11/12	1		ENSP00000386636.1	P05455
METTL5	ENST00000409837.5 linkuse as main transcript	c.592-955C>G		intron_variant		1		ENSP00000386703.1	B8ZZE3

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000186

AC:

AN:

231466

Hom.:

AF XY:

0.000247

AC XY:

AN XY:

125278

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000969

Gnomad EAS exome

AF:

0.000116

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000278

Gnomad OTH exome

AF:

0.000351

GnomAD4 exome

AF:

0.0000920

AC:

133

AN:

1445260

Hom.:

Cov.:

AF XY:

0.000129

AC XY:

AN XY:

718592

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000705

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000864

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000226

Gnomad4 OTH exome

AF:

0.000251

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.000173

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 30, 2024

The c.1114G>C (p.E372Q) alteration is located in exon 11 (coding exon 10) of the SSB gene. This alteration results from a G to C substitution at nucleotide position 1114, causing the glutamic acid (E) at amino acid position 372 to be replaced by a glutamine (Q). 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

0.11

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.27

T;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.26

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.40

.;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

0.0

N;N

REVEL

Benign

0.069

Sift

Benign

0.28

T;T

Sift4G

Benign

0.45

T;T

Polyphen

0.28

B;B

Vest4

0.24

MutPred

0.20

Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);

MVP

0.48

MPC

0.42

ClinPred

0.031

GERP RS

3.8

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.052

gMVP

0.18

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over