chr17-35352730-G-C

Position:

• chr17-35352730-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001376007.1(SLFN11):​c.2332C>G​(p.Arg778Gly) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R778Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: SLFN11 NM_001376007.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.77

Genes affected

SLFN11 (HGNC:26633): (schlafen family member 11) Enables tRNA binding activity. Involved in several processes, including defense response to virus; negative regulation of G1/S transition of mitotic cell cycle; and replication fork arrest. Located in cytosol; nucleoplasm; and site of DNA damage. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07516089).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLFN11	NM_001376007.1	c.2332C>G	p.Arg778Gly	missense_variant	7/7	ENST00000685675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLFN11	ENST00000685675.1	c.2332C>G	p.Arg778Gly	missense_variant	7/7		NM_001376007.1	P1
SLFN11	ENST00000308377.8	c.2332C>G	p.Arg778Gly	missense_variant	5/5	1		P1
SLFN11	ENST00000394566.5	c.2332C>G	p.Arg778Gly	missense_variant	7/7	2		P1
SLFN11	ENST00000592108.1	c.*141C>G		3_prime_UTR_variant	2/2	5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 30

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

Mar 29, 2022

The c.2332C>G (p.R778G) alteration is located in exon 7 (coding exon 4) of the SLFN11 gene. This alteration results from a C to G substitution at nucleotide position 2332, causing the arginine (R) at amino acid position 778 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	0.15
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.28
DANN	Benign	0.87
DEOGEN2	Benign	0.017	T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0053	N
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.075	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.17
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.027	D;D
Polyphen		0.0	B;B
Vest4		0.074
MutPred		0.37		Loss of MoRF binding (P = 0.0514);Loss of MoRF binding (P = 0.0514);
MVP		0.16
MPC		0.030
ClinPred		0.096	T
GERP RS		-5.9
Varity_R		0.11
gMVP		0.24

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: chr17-33679749;