rs183841255

Variant names:

• chr7-101239854-C-A
• rs183841255
• NM_016068.3:c.411G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-101239854-C-A
• chr7-101239854-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_016068.3(FIS1):​c.411G>T​(p.Ala137Ala) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A137A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FIS1 NM_016068.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.81
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25886315).
• BP7: Synonymous conserved (PhyloP=-3.81 with no splicing effect.

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.411G>T	p.Ala137Ala	synonymous	Exon 5 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.411G>T	p.Ala137Ala	synonymous	Exon 5 of 5	ENSP00000223136.4	Q9Y3D6
	FIS1	ENST00000474120.5	TSL:1	c.*67G>T		3_prime_UTR	Exon 4 of 4	ENSP00000442056.1	F5H8A8
	FIS1	ENST00000473527.5	TSL:1	n.*137G>T		non_coding_transcript_exon	Exon 5 of 5	ENSP00000444771.1	F5H509

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1456600 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724146

African (AFR) AF: 0.00 AC: 0 AN: 33382

American (AMR) AF: 0.00 AC: 0 AN: 44070

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25954

East Asian (EAS) AF: 0.00 AC: 0 AN: 39504

South Asian (SAS) AF: 0.00 AC: 0 AN: 85128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52864

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109806

Other (OTH) AF: 0.00 AC: 0 AN: 60128

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 2

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	0.053
DANN	Benign	0.95
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.61	T
PhyloP100		-3.8
PROVEAN	Pathogenic	-8.0	D
REVEL	Benign	0.061
MutPred		0.26		Loss of relative solvent accessibility (P = 0.0186)
MVP		0.50
ClinPred		0.95	D
GERP RS		-5.6
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Mutation Taster		=98/2	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

dbSNP: rs183841255; hg19: chr7-100883135;