NM_001321439.2:c.796G>C

Variant names:

• chr19-10923533-C-G
• rs746967829
• NM_001321439.2:c.796G>C

Variant summary

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

The NM_001321439.2(YIPF2):​c.796G>C​(p.Val266Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. V266F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: YIPF2 NM_001321439.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.760
• Publications: 0 publications found

Genes affected

YIPF2 (HGNC:28476): (Yip1 domain family member 2) Predicted to enable small GTPase binding activity. Predicted to be involved in vesicle-mediated transport. Located in Golgi apparatus subcompartment and transport vesicle. [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=0.21023023).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321439.2. 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
	YIPF2	NM_001321439.2	MANE Select	c.796G>C	p.Val266Leu	missense	Exon 8 of 10	NP_001308368.1	Q9BWQ6
	YIPF2	NM_024029.5		c.796G>C	p.Val266Leu	missense	Exon 8 of 10	NP_076934.1	Q9BWQ6
	YIPF2	NM_001321440.2		c.679G>C	p.Val227Leu	missense	Exon 7 of 9	NP_001308369.1	K7ENM8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YIPF2	ENST00000586748.6	TSL:1 MANE Select	c.796G>C	p.Val266Leu	missense	Exon 8 of 10	ENSP00000466055.1	Q9BWQ6
	YIPF2	ENST00000253031.6	TSL:1	c.796G>C	p.Val266Leu	missense	Exon 8 of 10	ENSP00000253031.1	Q9BWQ6
	YIPF2	ENST00000874113.1		c.796G>C	p.Val266Leu	missense	Exon 8 of 10	ENSP00000544172.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460256 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726522

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52192

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111754

Other (OTH) AF: 0.00 AC: 0 AN: 60362

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.45
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.76
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.084
Sift	Uncertain	0.012	D
Sift4G	Benign	0.19	T
Polyphen		0.51	P
Vest4		0.38
MutPred		0.35		Loss of catalytic residue at H270 (P = 0.5751)
MVP		0.095
MPC		0.19
ClinPred		0.48	T
GERP RS		2.5
PromoterAI		-0.0032	Neutral
Varity_R		0.13
gMVP		0.41
Mutation Taster		=78/22	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: rs746967829; hg19: chr19-11034209;