1-28237970-G-A

Variant names:

• chr1-28237970-G-A
• rs199945228
• NM_016311.5:c.313G>A

Variant summary

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

The NM_016311.5(ATP5IF1):​c.313G>A​(p.Asp105Asn) 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. 15/22 in silico tools predict a benign outcome for this variant. 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. D105Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP5IF1 NM_016311.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.76
• Publications: 1 publications found

Genes affected

ATP5IF1 (HGNC:871): (ATP synthase inhibitory factor subunit 1) Enables several functions, including ATPase binding activity; angiostatin binding activity; and mitochondrial proton-transporting ATP synthase complex binding activity. Involved in several processes, including mitochondrial depolarization; negative regulation of ATPase activity; and regulation of protein targeting to mitochondrion. Located in cell surface and mitochondrion. [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=0.1479182).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016311.5. 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
	ATP5IF1	NM_016311.5	MANE Select	c.313G>A	p.Asp105Asn	missense	Exon 3 of 3	NP_057395.1	Q9UII2-1
	ATP5IF1	NM_178190.3		c.*173G>A		3_prime_UTR	Exon 3 of 3	NP_835497.1	Q9UII2-2
	ATP5IF1	NM_178191.3		c.*1514G>A		3_prime_UTR	Exon 2 of 2	NP_835498.1	Q9UII2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP5IF1	ENST00000335514.10	TSL:1 MANE Select	c.313G>A	p.Asp105Asn	missense	Exon 3 of 3	ENSP00000335203.5	Q9UII2-1
	ATP5IF1	ENST00000465645.1	TSL:1	c.*1514G>A		3_prime_UTR	Exon 2 of 2	ENSP00000437337.1	Q9UII2-3
	ATP5IF1	ENST00000922360.1		c.355G>A	p.Asp119Asn	missense	Exon 4 of 4	ENSP00000592419.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.15	T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.8
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.23
Sift	Benign	0.093	T
Sift4G	Benign	0.086	T
Polyphen		0.035	B
Vest4		0.19
MutPred		0.13		Loss of ubiquitination at K100 (P = 0.0508)
MVP		0.94
MPC		0.76
ClinPred		0.65	D
GERP RS		3.0
Varity_R		0.049
gMVP		0.081
Mutation Taster		=89/11	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: rs199945228; hg19: chr1-28564481;