17-35411797-C-G

Position:

• chr17-35411797-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018042.5(SLFN12):​c.1278G>C​(p.Arg426Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLFN12 NM_018042.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.71

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35884607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLFN12	NM_018042.5	c.1278G>C	p.Arg426Ser	missense_variant	4/4	ENST00000304905.10
SLFN12	NM_001289009.2	c.1278G>C	p.Arg426Ser	missense_variant	4/4
SLFN12	XM_005257995.6	c.1278G>C	p.Arg426Ser	missense_variant	5/5
SLFN12	XM_024450822.2	c.1278G>C	p.Arg426Ser	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLFN12	ENST00000304905.10	c.1278G>C	p.Arg426Ser	missense_variant	4/4	1	NM_018042.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 01, 2024

The c.1278G>C (p.R426S) alteration is located in exon 4 (coding exon 3) of the SLFN12 gene. This alteration results from a G to C substitution at nucleotide position 1278, causing the arginine (R) at amino acid position 426 to be replaced by a serine (S). 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	Uncertain	0.44
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.34
DANN	Uncertain	0.98
DEOGEN2	Benign	0.30	T;T;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.75	.;.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;M;M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.5	D;D;D
REVEL	Benign	0.10
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		0.96	D;D;D
Vest4		0.32
MutPred		0.53		Loss of MoRF binding (P = 0.09);Loss of MoRF binding (P = 0.09);Loss of MoRF binding (P = 0.09);
MVP		0.11
MPC		0.21
ClinPred		0.96	D
GERP RS		-1.3
Varity_R		0.16
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-33738816;