7-101244976-G-C

Variant names:

• chr7-101244976-G-C
• rs772491435
• NM_016068.3:c.29C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1 PM2

The NM_016068.3(FIS1):​c.29C>G​(p.Ser10Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S10F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FIS1 NM_016068.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.26
• Publications: 2 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 4 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity FIS1_HUMAN
• PM2: Very rare variant in population databases, with high coverage

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.29C>G	p.Ser10Cys	missense	Exon 1 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.29C>G	p.Ser10Cys	missense	Exon 1 of 5	ENSP00000223136.4	Q9Y3D6
	FIS1	ENST00000474120.5	TSL:1	c.15-4070C>G		intron	N/A	ENSP00000442056.1	F5H8A8
	FIS1	ENST00000473527.5	TSL:1	n.15-837C>G		intron	N/A	ENSP00000444771.1	F5H509

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	31
DANN	Benign	0.91
DEOGEN2	Benign	0.21	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		6.3
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.57
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.027	D
Polyphen		0.99	D
Vest4		0.59
MutPred		0.46		Loss of disorder (P = 0.0079)
MVP		0.78
MPC		0.96
ClinPred		0.98	D
GERP RS		5.5
PromoterAI		-0.049	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.59
gMVP		0.49
Mutation Taster		=58/42	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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

dbSNP: rs772491435; hg19: chr7-100888257;