4-25802375-T-G

Position:

• chr4-25802375-T-G

Variant summary

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

The NM_015187.5(SEL1L3):​c.1864A>C​(p.Asn622His) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEL1L3 NM_015187.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.571

Genes affected

SEL1L3 (HGNC:29108): (SEL1L family member 3) Located in nucleoplasm. [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=0.07271996).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEL1L3	NM_015187.5	c.1864A>C	p.Asn622His	missense_variant	11/24	ENST00000399878.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEL1L3	ENST00000399878.8	c.1864A>C	p.Asn622His	missense_variant	11/24	1	NM_015187.5	P1
SEL1L3	ENST00000264868.9	c.1759A>C	p.Asn587His	missense_variant	11/24	1
SEL1L3	ENST00000502949.5	c.1405A>C	p.Asn469His	missense_variant	11/24	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Jun 06, 2023

The c.1864A>C (p.N622H) alteration is located in exon 11 (coding exon 11) of the SEL1L3 gene. This alteration results from a A to C substitution at nucleotide position 1864, causing the asparagine (N) at amino acid position 622 to be replaced by a histidine (H). 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	0.070
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	3.9
DANN	Benign	0.96
DEOGEN2	Benign	0.036	T;.;.
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.56	T;T;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.073	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.021
Sift	Benign	0.062	T;T;T
Sift4G	Benign	0.12	T;T;T
Polyphen		0.0010	B;.;.
Vest4		0.21
MutPred		0.41		Gain of catalytic residue at D621 (P = 0.1365);.;.;
MVP		0.14
MPC		0.19
ClinPred		0.16	T
GERP RS		-3.0
Varity_R		0.080
gMVP		0.22

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: chr4-25803997;