17-35478092-A-T

Position:

• chr17-35478092-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001363830.2(SLFN12L):​c.1259T>A​(p.Leu420Gln) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLFN12L NM_001363830.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.16

Genes affected

SLFN12L (HGNC:33920): (schlafen family member 12 like) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

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=0.25990692).
• BP6: Variant 17-35478092-A-T is Benign according to our data. Variant chr17-35478092-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2611541.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLFN12L	NM_001363830.2	c.1259T>A	p.Leu420Gln	missense_variant	4/5	ENST00000628453.4
SLFN12L	NM_001195790.3	c.1133T>A	p.Leu378Gln	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLFN12L	ENST00000628453.4	c.1259T>A	p.Leu420Gln	missense_variant	4/5	5	NM_001363830.2	A2
	ENST00000587076.1	n.99A>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2023

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	0.053
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.43
DANN	Benign	0.21
DEOGEN2	Benign	0.056	T;.;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00017	N
LIST_S2	Benign	0.43	T;T;.
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-2.3	N;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	2.1	N;N;.
REVEL	Benign	0.099
Sift	Benign	0.56	T;T;.
Sift4G	Benign	0.39	T;T;T
Polyphen		0.0030	.;B;.
Vest4		0.080
MutPred		0.81		.;Gain of disorder (P = 0.0405);.;
MVP		0.040
MPC		0.023
ClinPred		0.034	T
GERP RS		-1.6
Varity_R		0.059
gMVP		0.067

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: chr17-33805111;