chr17-35440788-A-C

Variant names:

• chr17-35440788-A-C
• rs751216867
• NM_144682.6:c.2501T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_144682.6(SLFN13):​c.2501T>G​(p.Met834Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLFN13 NM_144682.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.80
• Publications: 0 publications found

Genes affected

SLFN13 (HGNC:26481): (schlafen family member 13) Enables endoribonuclease activity. Involved in rRNA catabolic process and tRNA catabolic process. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.021673977).
• BP6: Variant 17-35440788-A-C is Benign according to our data. Variant chr17-35440788-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3320439.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLFN13	NM_144682.6	c.2501T>G	p.Met834Arg	missense_variant	Exon 6 of 6	ENST00000285013.11	NP_653283.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLFN13	ENST00000285013.11	c.2501T>G	p.Met834Arg	missense_variant	Exon 6 of 6	1	NM_144682.6	ENSP00000285013.6

Frequencies

GnomAD3 genomes AF: 0.0000988 AC: 15 AN: 151756 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000364

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

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251430 AF XY: 0.0000221

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1461796 Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12 AN XY: 727212

African (AFR) AF: 0.000150 AC: 5 AN: 33426

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000988 AC: 15 AN: 151874 Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7 AN XY: 74222

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000362 AC: 15 AN: 41382

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67952

Other (OTH) AF: 0.00 AC: 0 AN: 2106

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.011452), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000709 Hom.: 0

ExAC AF: 0.0000906 AC: 11

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

May 30, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.030
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.0040
DANN	Benign	0.11
DEOGEN2	Benign	0.00050	T;T;T;.;T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0022	N
LIST_S2	Benign	0.074	.;.;T;T;.
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.022	T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-2.4	N;N;N;.;N
PhyloP100		-1.8
PrimateAI	Benign	0.29	T
PROVEAN	Benign	2.6	N;N;N;N;.
REVEL	Benign	0.019
Sift	Benign	0.24	T;T;T;T;.
Sift4G	Benign	0.62	T;T;T;T;T
Polyphen		0.0	B;B;B;B;B
Vest4		0.10
MVP		0.14
MPC		0.050
ClinPred		0.064	T
GERP RS		-4.2
Varity_R		0.14
gMVP		0.086
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs751216867; hg19: chr17-33767807;