Variant chr17-35422118-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018042.5(SLFN12):c.911C>A(p.Ala304Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000263 in 152,138 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Consequence

SLFN12
NM_018042.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.101

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLFN12	NM_018042.5 link	c.911C>A	p.Ala304Glu	missense_variant	2/4	ENST00000304905.10	NP_060512.3	Q8IYM2
SLFN12	NM_001289009.2 link	c.911C>A	p.Ala304Glu	missense_variant	2/4		NP_001275938.1	Q8IYM2
SLFN12	XM_005257995.6 link	c.911C>A	p.Ala304Glu	missense_variant	3/5		XP_005258052.1	Q8IYM2
SLFN12	XM_024450822.2 link	c.911C>A	p.Ala304Glu	missense_variant	4/6		XP_024306590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLFN12	ENST00000304905.10 link	c.911C>A	p.Ala304Glu	missense_variant	2/4	1	NM_018042.5	ENSP00000302077.5	Q8IYM2
SLFN12	ENST00000394562.5 link	c.911C>A	p.Ala304Glu	missense_variant	4/6	1		ENSP00000378063.1	Q8IYM2
SLFN12	ENST00000452764.3 link	c.911C>A	p.Ala304Glu	missense_variant	2/4	2		ENSP00000394903.2	Q8IYM2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000354

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

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

Aug 01, 2022

The c.911C>A (p.A304E) alteration is located in exon 2 (coding exon 1) of the SLFN12 gene. This alteration results from a C to A substitution at nucleotide position 911, causing the alanine (A) at amino acid position 304 to be replaced by a glutamic acid (E). 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

Pathogenic

0.85

BayesDel_addAF

Uncertain

0.089

BayesDel_noAF

Benign

-0.11

CADD

Benign

8.2

DANN

Benign

0.97

DEOGEN2

Benign

0.16

T;T;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.74

.;.;T

M_CAP

Benign

0.070

MetaRNN

Uncertain

0.71

D;D;D

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.7

M;M;M

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.6

D;D;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.014

D;D;D

Sift4G

Uncertain

0.023

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.61

MVP

0.39

MPC

0.34

ClinPred

0.91

GERP RS

-2.3

Varity_R

0.37

gMVP

0.75

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