rs776647622

Variant names:

• chr17-35352498-C-G
• NM_001376007.1:c.2564G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-35352498-C-G
• chr17-35352498-C-T

Variant summary

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

The NM_001376007.1(SLFN11):​c.2564G>C​(p.Arg855Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R855Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLFN11 NM_001376007.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.522

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLFN11	NM_001376007.1	c.2564G>C	p.Arg855Pro	missense_variant	Exon 7 of 7	ENST00000685675.1	NP_001362936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLFN11	ENST00000685675.1	c.2564G>C	p.Arg855Pro	missense_variant	Exon 7 of 7		NM_001376007.1	ENSP00000510787.1
SLFN11	ENST00000308377.8	c.2564G>C	p.Arg855Pro	missense_variant	Exon 5 of 5	1		ENSP00000312402.4
SLFN11	ENST00000394566.5	c.2564G>C	p.Arg855Pro	missense_variant	Exon 7 of 7	2		ENSP00000378067.1
SLFN11	ENST00000592108	c.*373G>C		3_prime_UTR_variant	Exon 2 of 2	5		ENSP00000465198.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;T
Eigen	Benign	-0.016
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.69	.;T
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Pathogenic	2.9	M;M
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Uncertain	0.48
Sift	Uncertain	0.027	D;D
Sift4G	Uncertain	0.012	D;D
Polyphen		1.0	D;D
Vest4		0.58
MutPred		0.52		Gain of loop (P = 0.069);Gain of loop (P = 0.069);
MVP		0.55
MPC		0.24
ClinPred		0.98	D
GERP RS		2.0
Varity_R		0.68
gMVP		0.49

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: chr17-33679517;