dbSNP rs3816668: BLK:p.Ser110Arg (chr8-11549084-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001715.3(BLK):c.330T>A(p.Ser110Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,128 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S110N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BLK
NM_001715.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.386

Publications

0 publications found

Variant links:

Genes affected

BLK (HGNC:1057): (BLK proto-oncogene, Src family tyrosine kinase) This gene encodes a nonreceptor tyrosine-kinase of the src family of proto-oncogenes that are typically involved in cell proliferation and differentiation. The protein has a role in B-cell receptor signaling and B-cell development. The protein also stimulates insulin synthesis and secretion in response to glucose and enhances the expression of several pancreatic beta-cell transcription factors. [provided by RefSeq, Aug 2010]

BLK Gene-Disease associations (from GenCC):

maturity-onset diabetes of the young
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
maturity-onset diabetes of the young type 11
Inheritance: AD, Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
monogenic diabetes
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

BLK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLK	NM_001715.3 link	c.330T>A	p.Ser110Arg	missense_variant	Exon 5 of 13	ENST00000259089.9	NP_001706.2	P51451Q05D26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BLK	ENST00000259089.9 link	c.330T>A	p.Ser110Arg	missense_variant	Exon 5 of 13	1	NM_001715.3	ENSP00000259089.4	P51451
BLK	ENST00000533828.1 link	n.528T>A		non_coding_transcript_exon_variant	Exon 3 of 3	4
BLK	ENST00000645242.1 link	n.481T>A		non_coding_transcript_exon_variant	Exon 4 of 12
BLK	ENST00000696154.2 link	n.481T>A		non_coding_transcript_exon_variant	Exon 4 of 12				A0A8Q3SIE3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458128

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724758

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33452

American (AMR)

AF:

0.00

AC:

AN:

44226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26066

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

85078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53214

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1110360

Other (OTH)

AF:

0.00

AC:

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Uncertain

0.025

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

T;T;T

Eigen

Benign

0.0085

Eigen_PC

Benign

-0.098

FATHMM_MKL

Benign

0.33

LIST_S2

Uncertain

0.93

.;D;.

M_CAP

Benign

0.042

MetaRNN

Uncertain

0.68

D;D;D

MetaSVM

Benign

-0.48

MutationAssessor

Benign

2.0

.;M;.

PhyloP100

-0.39

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-4.0

.;D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.012

.;D;D

Sift4G

Benign

0.16

.;T;T

Polyphen

0.99

.;D;.

Vest4

0.49, 0.47

MutPred

0.63

.;Gain of MoRF binding (P = 0.0456);.;

MVP

0.78

MPC

0.18

ClinPred

0.98

GERP RS

3.2

Varity_R

0.43

gMVP

0.68

Mutation Taster

=75/25

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over