7-101244027-T-C

Variant names:

• chr7-101244027-T-C
• NM_016068.3:c.158A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016068.3(FIS1):​c.158A>G​(p.Lys53Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FIS1 NM_016068.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.61
• Publications: 0 publications found

Genes affected

FIS1 (HGNC:21689): (fission, mitochondrial 1) Enables identical protein binding activity. Involved in several processes, including calcium-mediated signaling using intracellular calcium source; cellular calcium ion homeostasis; and mitochondrion organization. Acts upstream of or within mitochondrion morphogenesis. Located in mitochondrion and peroxisome. Is integral component of mitochondrial outer membrane and integral component of peroxisomal membrane. Part of protein-containing complex. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20207831).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016068.3. 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
	FIS1	NM_016068.3	MANE Select	c.158A>G	p.Lys53Arg	missense	Exon 2 of 5	NP_057152.2	Q9Y3D6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FIS1	ENST00000223136.5	TSL:1 MANE Select	c.158A>G	p.Lys53Arg	missense	Exon 2 of 5	ENSP00000223136.4	Q9Y3D6
	FIS1	ENST00000474120.5	TSL:1	c.15-3121A>G		intron	N/A	ENSP00000442056.1	F5H8A8
	FIS1	ENST00000473527.5	TSL:1	n.127A>G		non_coding_transcript_exon	Exon 2 of 5	ENSP00000444771.1	F5H509

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.080
BayesDel_addAF	Benign	0.0036	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
PhyloP100		3.6
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.23
MutPred		0.20		Loss of MoRF binding (P = 0.0047)
MVP		0.65
ClinPred		0.55	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
Mutation Taster		=73/27	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: chr7-100887308;