rs377577583

Variant names:

• chrX-54440443-G-A
• rs377577583
• NM_058163.3:c.22G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-54440443-G-A
• chrX-54440443-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_058163.3(TSR2):​c.22G>A​(p.Ala8Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000197 in 1,014,800 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000020 (0 hom. 0 hem.)
• Consequence: TSR2 NM_058163.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.653

Genes affected

TSR2 (HGNC:25455): (TSR2 ribosome maturation factor) The protein encoded by this gene appears to repress the transcription of NF-kappaB and may be involved in apoptosis. Defects in this gene are a cause of Diamond-Blackfan anemia. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03714934).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSR2	NM_058163.3	c.22G>A	p.Ala8Thr	missense_variant	Exon 1 of 5	ENST00000375151.5	NP_477511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSR2	ENST00000375151.5	c.22G>A	p.Ala8Thr	missense_variant	Exon 1 of 5	1	NM_058163.3	ENSP00000364293.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000197 AC: 2 AN: 1014800 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 319730

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: 0.0000238

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000124

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ExAC AF: 0.0000170 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.8
DANN	Benign	0.80
DEOGEN2	Benign	0.027	T
FATHMM_MKL	Benign	0.00037	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.021
Sift	Benign	0.48	T
Sift4G	Benign	0.31	T
Polyphen		0.0	B
Vest4		0.070
MutPred		0.37		Gain of glycosylation at A8 (P = 0.0634);
MVP		0.12
MPC		0.52
ClinPred		0.034	T
GERP RS		-0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.039
gMVP		0.14

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

Other links and lift over

dbSNP: rs377577583; hg19: chrX-54466876;