Variant chr17-35475320-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001363830.2(SLFN12L):c.1442A>G(p.His481Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,614,112 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: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

SLFN12L
NM_001363830.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.506

Variant links:

Genes affected

SLFN12L (HGNC:33920): (schlafen family member 12 like) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLFN12L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.056493223).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLFN12L	NM_001363830.2 linkuse as main transcript	c.1442A>G	p.His481Arg	missense_variant	5/5	ENST00000628453.4
SLFN12L	NM_001195790.3 linkuse as main transcript	c.1316A>G	p.His439Arg	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SLFN12L	ENST00000628453.4 linkuse as main transcript	c.1442A>G	p.His481Arg	missense_variant	5/5	5	NM_001363830.2	A2
SLFN12L	ENST00000260908.13 linkuse as main transcript	c.1316A>G	p.His439Arg	missense_variant	4/4	5		P2
SLFN12L	ENST00000587436.1 linkuse as main transcript	n.395+2755A>G		intron_variant, non_coding_transcript_variant		2
SLFN12L	ENST00000590802.1 linkuse as main transcript	n.152+2755A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251278

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

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:

0.0000264

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.0000308

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

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:

0.0000234

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000109

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

Jun 28, 2022

The c.1370A>G (p.H457R) alteration is located in exon 4 (coding exon 4) of the SLFN12L gene. This alteration results from a A to G substitution at nucleotide position 1370, causing the histidine (H) at amino acid position 457 to be replaced by an arginine (R). 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

0.064

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.6

DANN

Benign

0.84

DEOGEN2

Benign

0.046

T;.;T

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.42

T;T;.

M_CAP

Benign

0.0020

MetaRNN

Benign

0.056

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.69

N;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.20

N;N;.

REVEL

Benign

0.027

Sift

Benign

0.18

T;T;.

Sift4G

Benign

0.17

T;T;T

Polyphen

0.12

.;B;.

Vest4

0.070

MutPred

0.41

.;Gain of ubiquitination at K487 (P = 0.0954);.;

MVP

0.014

MPC

0.025

ClinPred

0.023

GERP RS

1.1

Varity_R

0.028

gMVP

0.084

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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