Variant 17-35422223-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_018042.5(SLFN12):c.806G>A(p.Arg269Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

SLFN12
NM_018042.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.40

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026259392).

BP6

Variant 17-35422223-C-T is Benign according to our data. Variant chr17-35422223-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2478296.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLFN12	NM_018042.5 linkuse as main transcript	c.806G>A	p.Arg269Lys	missense_variant	2/4	ENST00000304905.10	NP_060512.3	Q8IYM2
SLFN12	NM_001289009.2 linkuse as main transcript	c.806G>A	p.Arg269Lys	missense_variant	2/4		NP_001275938.1	Q8IYM2
SLFN12	XM_005257995.6 linkuse as main transcript	c.806G>A	p.Arg269Lys	missense_variant	3/5		XP_005258052.1	Q8IYM2
SLFN12	XM_024450822.2 linkuse as main transcript	c.806G>A	p.Arg269Lys	missense_variant	4/6		XP_024306590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLFN12	ENST00000304905.10 linkuse as main transcript	c.806G>A	p.Arg269Lys	missense_variant	2/4	1	NM_018042.5	ENSP00000302077.5	Q8IYM2
SLFN12	ENST00000394562.5 linkuse as main transcript	c.806G>A	p.Arg269Lys	missense_variant	4/6	1		ENSP00000378063.1	Q8IYM2
SLFN12	ENST00000452764.3 linkuse as main transcript	c.806G>A	p.Arg269Lys	missense_variant	2/4	2		ENSP00000394903.2	Q8IYM2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251368

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135876

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:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727214

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:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.0030

DANN

Benign

0.48

DEOGEN2

Benign

0.0028

T;T;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.22

.;.;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.026

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.13

N;N;N

REVEL

Benign

0.017

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.83

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.036

MutPred

0.37

Gain of methylation at R269 (P = 0.0047);Gain of methylation at R269 (P = 0.0047);Gain of methylation at R269 (P = 0.0047);

MVP

0.27

MPC

0.050

ClinPred

0.020

GERP RS

-7.0

Varity_R

0.020

gMVP

0.32

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