Variant 12-121805128-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_001353345.2(SETD1B):c.185A>G(p.Asn62Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,399,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

SETD1B
NM_001353345.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.75

Variant links:

Genes affected

SETD1B (HGNC:29187): (SET domain containing 1B, histone lysine methyltransferase) SET1B is a component of a histone methyltransferase complex that produces trimethylated histone H3 at Lys4 (Lee et al., 2007 [PubMed 17355966]).[supplied by OMIM, Mar 2008]

SETD1B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SETD1B. . Trascript score misZ 3.1492 (greater than threshold 3.09). GenCC has associacion of gene with intellectual developmental disorder with seizures and language delay.

BP4

Computational evidence support a benign effect (MetaRNN=0.13936281).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SETD1B	NM_001353345.2 linkuse as main transcript	c.185A>G	p.Asn62Ser	missense_variant	3/17	ENST00000604567.6	NP_001340274.1
SETD1B	XM_024448898.2 linkuse as main transcript	c.185A>G	p.Asn62Ser	missense_variant	3/17		XP_024304666.1
SETD1B	XM_047428552.1 linkuse as main transcript	c.185A>G	p.Asn62Ser	missense_variant	3/17		XP_047284508.1
SETD1B	XM_047428553.1 linkuse as main transcript	c.185A>G	p.Asn62Ser	missense_variant	3/17		XP_047284509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SETD1B	ENST00000604567.6 linkuse as main transcript	c.185A>G	p.Asn62Ser	missense_variant	3/17	5	NM_001353345.2	ENSP00000474253.1	Q9UPS6-1
SETD1B	ENST00000619791.1 linkuse as main transcript	c.185A>G	p.Asn62Ser	missense_variant	2/16	1		ENSP00000481531.1	Q9UPS6-1
SETD1B	ENST00000542440.5 linkuse as main transcript	c.185A>G	p.Asn62Ser	missense_variant	3/18	5		ENSP00000442924.1	Q9UPS6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1399352

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690180

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Intellectual developmental disorder with seizures and language delay

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

MGZ Medical Genetics Center

Apr 26, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Benign

0.89

DEOGEN2

Benign

0.0056

T;.;T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.79

.;T;T;T

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-0.43

MutationAssessor

Benign

-0.46

N;N;.;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.36

.;N;N;.

REVEL

Benign

0.24

Sift

Benign

0.41

.;T;T;.

Sift4G

Benign

0.35

T;T;T;T

Polyphen

0.55

P;.;.;P

Vest4

0.25

MutPred

0.36

Gain of disorder (P = 0.0388);Gain of disorder (P = 0.0388);Gain of disorder (P = 0.0388);Gain of disorder (P = 0.0388);

MVP

0.56

MPC

1.5

ClinPred

0.27

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.057

gMVP

0.69

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over