17-43013614-C-G

Variant names:

• chr17-43013614-C-G
• rs369228705
• NM_001330230.2:c.514C>G

Variant summary

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

The NM_001330230.2(IFI35):​c.514C>G​(p.Arg172Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R172Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IFI35 NM_001330230.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58
• Publications: 0 publications found

Genes affected

IFI35 (HGNC:5399): (interferon induced protein 35) Enables identical protein binding activity. Involved in several processes, including macrophage activation involved in immune response; positive regulation of defense response; and regulation of signal transduction. Located in several cellular components, including cytosol; extracellular space; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

VAT1 (HGNC:16919): (vesicle amine transport 1) Synaptic vesicles are responsible for regulating the storage and release of neurotransmitters in the nerve terminal. The protein encoded by this gene is an abundant integral membrane protein of cholinergic synaptic vesicles and is thought to be involved in vesicular transport. It belongs to the quinone oxidoreductase subfamily of zinc-containing alcohol dehydrogenase proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330230.2. 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
	IFI35	NM_001330230.2	MANE Select	c.514C>G	p.Arg172Gly	missense	Exon 5 of 7	NP_001317159.1	P80217-1
	IFI35	NM_005533.5		c.520C>G	p.Arg174Gly	missense	Exon 5 of 7	NP_005524.2	P80217-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFI35	ENST00000415816.7	TSL:5 MANE Select	c.514C>G	p.Arg172Gly	missense	Exon 5 of 7	ENSP00000394579.3	P80217-1
	IFI35	ENST00000438323.2	TSL:1	c.520C>G	p.Arg174Gly	missense	Exon 5 of 7	ENSP00000395590.2	P80217-2
	VAT1	ENST00000943217.1		c.*1+2446G>C		intron	N/A	ENSP00000613276.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461848 Hom.: 0 Cov.: 39 AF XY: 0.00000138 AC XY: 1 AN XY: 727220

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.020
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		1.6
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.31
Sift	Benign	0.22	T
Sift4G	Benign	0.074	T
Polyphen		1.0	D
Vest4		0.66
MutPred		0.45		Gain of sheet (P = 0.0827)
MVP		0.55
MPC		0.45
ClinPred		0.96	D
GERP RS		4.0
Varity_R		0.72
gMVP		0.74
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs369228705; hg19: chr17-41165631;