Variant chr17-35422194-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018042.5(SLFN12):c.835G>C(p.Glu279Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SLFN12
NM_018042.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.27

Variant links:

Genes affected

SLFN12 (HGNC:25500): (schlafen family member 12) Predicted to act upstream of or within negative regulation of cell population proliferation. [provided by Alliance of Genome Resources, Apr 2022]

SLFN12 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12828624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLFN12	NM_018042.5 link	c.835G>C	p.Glu279Gln	missense_variant	2/4	ENST00000304905.10	NP_060512.3	Q8IYM2
SLFN12	NM_001289009.2 link	c.835G>C	p.Glu279Gln	missense_variant	2/4		NP_001275938.1	Q8IYM2
SLFN12	XM_005257995.6 link	c.835G>C	p.Glu279Gln	missense_variant	3/5		XP_005258052.1	Q8IYM2
SLFN12	XM_024450822.2 link	c.835G>C	p.Glu279Gln	missense_variant	4/6		XP_024306590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLFN12	ENST00000304905.10 link	c.835G>C	p.Glu279Gln	missense_variant	2/4	1	NM_018042.5	ENSP00000302077.5	Q8IYM2
SLFN12	ENST00000394562.5 link	c.835G>C	p.Glu279Gln	missense_variant	4/6	1		ENSP00000378063.1	Q8IYM2
SLFN12	ENST00000452764.3 link	c.835G>C	p.Glu279Gln	missense_variant	2/4	2		ENSP00000394903.2	Q8IYM2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251412

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135880

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461816

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727200

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Dec 04, 2024

The c.835G>C (p.E279Q) alteration is located in exon 2 (coding exon 1) of the SLFN12 gene. This alteration results from a G to C substitution at nucleotide position 835, causing the glutamic acid (E) at amino acid position 279 to be replaced by a glutamine (Q). 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

Benign

0.14

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.0050

DANN

Benign

0.26

DEOGEN2

Benign

0.0064

T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.62

.;.;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.5

L;L;L

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.81

N;N;N

REVEL

Benign

0.049

Sift

Benign

0.57

T;T;T

Sift4G

Benign

0.29

T;T;T

Polyphen

0.41

B;B;B

Vest4

0.094

MutPred

0.46

Loss of solvent accessibility (P = 0.0174);Loss of solvent accessibility (P = 0.0174);Loss of solvent accessibility (P = 0.0174);

MVP

0.36

MPC

0.088

ClinPred

0.086

GERP RS

-2.5

Varity_R

0.028

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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