Variant chr17-35420339-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_018042.5(SLFN12):c.1082C>T(p.Thr361Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000529 in 1,613,684 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00055 ( 4 hom. )

Consequence

SLFN12
NM_018042.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.30

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 17-35420339-G-A is Benign according to our data. Variant chr17-35420339-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2373187.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLFN12	NM_018042.5 linkuse as main transcript	c.1082C>T	p.Thr361Met	missense_variant	3/4	ENST00000304905.10
SLFN12	NM_001289009.2 linkuse as main transcript	c.1082C>T	p.Thr361Met	missense_variant	3/4
SLFN12	XM_005257995.6 linkuse as main transcript	c.1082C>T	p.Thr361Met	missense_variant	4/5
SLFN12	XM_024450822.2 linkuse as main transcript	c.1082C>T	p.Thr361Met	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLFN12	ENST00000304905.10 linkuse as main transcript	c.1082C>T	p.Thr361Met	missense_variant	3/4	1	NM_018042.5	P1

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000948

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000259

AC:

AN:

251274

Hom.:

AF XY:

0.000243

AC XY:

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000457

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000553

AC:

808

AN:

1461498

Hom.:

Cov.:

AF XY:

0.000495

AC XY:

360

AN XY:

727058

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

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:

0.000131

Gnomad4 NFE exome

AF:

0.000659

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.000296

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000948

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000387

Hom.:

Bravo

AF:

0.000348

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000198

AC:

EpiCase

AF:

0.000437

EpiControl

AF:

0.000474

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

Jun 21, 2022

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

0.093

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.9

DANN

Benign

0.63

DEOGEN2

Benign

0.0032

T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00066

LIST_S2

Benign

0.38

.;.;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.026

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.44

N;N;N

REVEL

Benign

0.0040

Sift

Benign

0.14

T;T;T

Sift4G

Benign

0.15

T;T;T

Polyphen

0.0020

B;B;B

Vest4

0.082

MVP

0.040

MPC

0.051

ClinPred

0.0018

GERP RS

-2.2

Varity_R

0.013

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.28

Position offset: -22

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