chr17-35479590-T-A

Position:

• chr17-35479590-T-A

Variant summary

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

The NM_001363830.2(SLFN12L):​c.692A>T​(p.Glu231Val) 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. 14/21 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. E231K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLFN12L NM_001363830.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.21

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]

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=0.22542506).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLFN12L	NM_001363830.2	c.692A>T	p.Glu231Val	missense_variant	3/5	ENST00000628453.4
SLFN12L	NM_001195790.3	c.566A>T	p.Glu189Val	missense_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLFN12L	ENST00000628453.4	c.692A>T	p.Glu231Val	missense_variant	3/5	5	NM_001363830.2	A2
SLFN12L	ENST00000260908.13	c.566A>T	p.Glu189Val	missense_variant	2/4	5		P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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

Jan 03, 2024

The c.620A>T (p.E207V) alteration is located in exon 2 (coding exon 2) of the SLFN12L gene. This alteration results from a A to T substitution at nucleotide position 620, causing the glutamic acid (E) at amino acid position 207 to be replaced by a valine (V). 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	0.14
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.48
DANN	Benign	0.27
DEOGEN2	Benign	0.29	T;.;T
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.43	T;T;.
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.3	L;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.0	D;D;.
REVEL	Benign	0.0070
Sift	Benign	0.049	D;T;.
Sift4G	Benign	0.51	T;T;T
Polyphen		0.35	.;B;.
Vest4		0.14
MutPred		0.32		.;Loss of disorder (P = 0.0471);.;
MVP		0.072
MPC		0.041
ClinPred		0.31	T
GERP RS		-1.1
Varity_R		0.12
gMVP		0.11

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: chr17-33806609;