2-169811284-GATGATGAAC-G

Position:

• chr2-169811284-GATGATGAAC-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_003142.5(SSB):​c.1117_1125delCATGATGAA​(p.His373_Glu375del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00411 in 1,609,030 control chromosomes in the GnomAD database, including 15 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (14 hom.)
• Consequence: SSB NM_003142.5 conservative_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0890

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]

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 2-169811284-GATGATGAAC-G is Benign according to our data. Variant chr2-169811284-GATGATGAAC-G is described in ClinVar as [Likely_benign]. Clinvar id is 3341507.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 516 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSB	NM_003142.5	c.1117_1125delCATGATGAA	p.His373_Glu375del	conservative_inframe_deletion	11/12	ENST00000260956.9	NP_003133.1
SSB	NM_001294145.2	c.1117_1125delCATGATGAA	p.His373_Glu375del	conservative_inframe_deletion	11/12		NP_001281074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSB	ENST00000260956.9	c.1117_1125delCATGATGAA	p.His373_Glu375del	conservative_inframe_deletion	11/12	1	NM_003142.5	ENSP00000260956.4
SSB	ENST00000409333.1	c.1117_1125delCATGATGAA	p.His373_Glu375del	conservative_inframe_deletion	11/12	1		ENSP00000386636.1
METTL5	ENST00000409837.5	c.592-949_592-941delGTTCATCAT		intron_variant		1		ENSP00000386703.1

Frequencies

GnomAD3 genomes AF: 0.00340 AC: 517 AN: 152130 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00537

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00123

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00485

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00290 AC: 713 AN: 245622 Hom.: 2 AF XY: 0.00298 AC XY: 395 AN XY: 132680

Gnomad AFR exome AF: 0.000868

Gnomad AMR exome AF: 0.00277

Gnomad ASJ exome AF: 0.00383

Gnomad EAS exome AF: 0.000165

Gnomad SAS exome AF: 0.00163

Gnomad FIN exome AF: 0.00107

Gnomad NFE exome AF: 0.00422

Gnomad OTH exome AF: 0.00399

GnomAD4 exome AF: 0.00418 AC: 6092 AN: 1456782 Hom.: 14 AF XY: 0.00421 AC XY: 3049 AN XY: 724544

Gnomad4 AFR exome AF: 0.000813

Gnomad4 AMR exome AF: 0.00339

Gnomad4 ASJ exome AF: 0.00484

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.00194

Gnomad4 FIN exome AF: 0.00118

Gnomad4 NFE exome AF: 0.00472

Gnomad4 OTH exome AF: 0.00443

GnomAD4 genome AF: 0.00339 AC: 516 AN: 152248 Hom.: 1 Cov.: 32 AF XY: 0.00328 AC XY: 244 AN XY: 74450

Gnomad4 AFR AF: 0.00128

Gnomad4 AMR AF: 0.00536

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00123

Gnomad4 NFE AF: 0.00485

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00186 Hom.: 0

Bravo AF: 0.00394

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2024

SSB: PM4, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs568710324; hg19: chr2-170667794;