Variant chr17-35422457-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_018042.5(SLFN12):c.572A>G(p.Asp191Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,202 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 0.0000066 ( 0 hom., cov: 33)

Consequence

SLFN12
NM_018042.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.26

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.056767583).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLFN12	NM_018042.5 linkuse as main transcript	c.572A>G	p.Asp191Gly	missense_variant	2/4	ENST00000304905.10
SLFN12	NM_001289009.2 linkuse as main transcript	c.572A>G	p.Asp191Gly	missense_variant	2/4
SLFN12	XM_005257995.6 linkuse as main transcript	c.572A>G	p.Asp191Gly	missense_variant	3/5
SLFN12	XM_024450822.2 linkuse as main transcript	c.572A>G	p.Asp191Gly	missense_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SLFN12	ENST00000304905.10 linkuse as main transcript	c.572A>G	p.Asp191Gly	missense_variant	2/4	1	NM_018042.5	P1
SLFN12	ENST00000394562.5 linkuse as main transcript	c.572A>G	p.Asp191Gly	missense_variant	4/6	1		P1
SLFN12	ENST00000452764.3 linkuse as main transcript	c.572A>G	p.Asp191Gly	missense_variant	2/4	2		P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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

Bravo

AF:

0.0000113

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 29, 2023

The c.572A>G (p.D191G) alteration is located in exon 2 (coding exon 1) of the SLFN12 gene. This alteration results from a A to G substitution at nucleotide position 572, causing the aspartic acid (D) at amino acid position 191 to be replaced by a glycine (G). 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

0.091

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.0010

DANN

Benign

0.67

DEOGEN2

Benign

0.0075

T;T;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0050

LIST_S2

Benign

0.081

.;.;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.057

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.69

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.010

Sift

Benign

0.20

T;T;T

Sift4G

Benign

0.37

T;T;T

Polyphen

0.022

B;B;B

Vest4

0.15

MVP

0.072

MPC

0.061

ClinPred

0.080

GERP RS

-6.6

Varity_R

0.031

gMVP

0.27

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