chr1-41016132-C-T

Variant names:

• chr1-41016132-C-T
• NM_144990.4:c.1198G>A

Variant summary

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

The NM_144990.4(SLFNL1):​c.1198G>A​(p.Val400Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,772 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLFNL1 NM_144990.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.50
• Publications: 0 publications found

Genes affected

SLFNL1 (HGNC:26313): (schlafen like 1) Predicted to enable ATP binding activity. [provided by Alliance of Genome Resources, Apr 2022]

SLFNL1-AS1 (HGNC:44126): (SLFNL1 antisense RNA 1)

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=0.03840506).
• BP6: Variant 1-41016132-C-T is Benign according to our data. Variant chr1-41016132-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3320480.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144990.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLFNL1	NM_144990.4	MANE Select	c.1198G>A	p.Val400Met	missense	Exon 6 of 6	NP_659427.3
	SLFNL1	NM_001168247.3		c.1198G>A	p.Val400Met	missense	Exon 6 of 6	NP_001161719.1	Q499Z3-1
	SLFNL1	NM_001377532.1		c.1198G>A	p.Val400Met	missense	Exon 4 of 4	NP_001364461.1	Q499Z3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLFNL1	ENST00000302946.13	TSL:1 MANE Select	c.1198G>A	p.Val400Met	missense	Exon 6 of 6	ENSP00000304401.8	Q499Z3-1
	SLFNL1	ENST00000359345.5	TSL:1	c.1198G>A	p.Val400Met	missense	Exon 4 of 4	ENSP00000352299.1	Q499Z3-1
	SLFNL1-AS1	ENST00000626479.1	TSL:1	n.1543C>T		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461772 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727180

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111946

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.023
DANN	Benign	0.72
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		-3.5
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.0040
Sift	Benign	0.16	T
Sift4G	Uncertain	0.050	T
Polyphen		0.53	P
Vest4		0.072
MutPred		0.20		Loss of sheet (P = 0.0817)
MVP		0.014
MPC		0.051
ClinPred		0.15	T
GERP RS		-9.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.024
gMVP		0.20
Mutation Taster		=96/4	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

hg19: chr1-41481804;