Variant 19-50428047-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_003121.5(SPIB):c.500A>C(p.Lys167Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000436 in 1,376,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

SPIB
NM_003121.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.13

Variant links:

Genes affected

SPIB (HGNC:11242): (Spi-B transcription factor) The protein encoded by this gene is a transcriptional activator that binds to the PU-box (5'-GAGGAA-3') and acts as a lymphoid-specific enhancer. Four transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

SPIB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3172087).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SPIB	NM_003121.5 linkuse as main transcript	c.500A>C	p.Lys167Thr	missense_variant	6/6	ENST00000595883.6
SPIB	NM_001244000.2 linkuse as main transcript	c.407A>C	p.Lys136Thr	missense_variant	6/6
SPIB	NM_001243998.2 linkuse as main transcript	c.227A>C	p.Lys76Thr	missense_variant	5/5
SPIB	NM_001243999.2 linkuse as main transcript	c.496A>C	p.Arg166=	synonymous_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPIB	ENST00000595883.6 linkuse as main transcript	c.500A>C	p.Lys167Thr	missense_variant	6/6	1	NM_003121.5	P1	Q01892-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000658

AC:

AN:

151964

Hom.:

AF XY:

0.0000123

AC XY:

AN XY:

81106

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000163

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000436

AC:

AN:

1376644

Hom.:

Cov.:

AF XY:

0.00000592

AC XY:

AN XY:

675440

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000564

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000849

AC:

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

Feb 14, 2023

The c.500A>C (p.K167T) alteration is located in exon 1 (coding exon 1) of the SPIB gene. This alteration results from a A to C substitution at nucleotide position 500, causing the lysine (K) at amino acid position 167 to be replaced by a threonine (T). 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

0.89

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.42

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.97

D;D

M_CAP

Benign

0.046

MetaRNN

Benign

0.32

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.90

D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-5.0

D;.

REVEL

Benign

0.11

Sift

Benign

0.12

T;.

Sift4G

Uncertain

0.0070

D;D

Polyphen

0.98

.;D

Vest4

0.42

MutPred

0.42

.;Loss of methylation at K167 (P = 0.0071);

MVP

0.39

MPC

2.9

ClinPred

0.96

GERP RS

3.8

Varity_R

0.19

gMVP

0.91

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