1-28237892-G-T

Variant names:

• chr1-28237892-G-T
• rs758401235
• NM_016311.5:c.235G>T

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.235G>T​(p.Val79Phe) 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. 14/22 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. V79I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ATP5IF1 NM_016311.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313
• 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=0.10568562).

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.235G>T	p.Val79Phe	missense	Exon 3 of 3	NP_057395.1	Q9UII2-1
	ATP5IF1	NM_178190.3		c.*95G>T		3_prime_UTR	Exon 3 of 3	NP_835497.1	Q9UII2-2
	ATP5IF1	NM_178191.3		c.*1436G>T		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.235G>T	p.Val79Phe	missense	Exon 3 of 3	ENSP00000335203.5	Q9UII2-1
	ATP5IF1	ENST00000465645.1	TSL:1	c.*1436G>T		3_prime_UTR	Exon 2 of 2	ENSP00000437337.1	Q9UII2-3
	ATP5IF1	ENST00000922360.1		c.277G>T	p.Val93Phe	missense	Exon 4 of 4	ENSP00000592419.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	0.26
DANN	Benign	0.97
DEOGEN2	Benign	0.071	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.11	N
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.31
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.65	N
REVEL	Uncertain	0.32
Sift	Benign	0.052	T
Sift4G	Benign	0.075	T
Polyphen		0.15	B
Vest4		0.28
MutPred		0.33		Loss of MoRF binding (P = 0.0924)
MVP		0.66
MPC		0.57
ClinPred		0.32	T
GERP RS		-8.7
Varity_R		0.062
gMVP		0.085
Mutation Taster		=96/4	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: rs758401235; hg19: chr1-28564403;