rs778397143

Variant names:

• chr19-10923877-C-T
• rs778397143
• NM_001321439.2:c.607G>A

Variant summary

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

The NM_001321439.2(YIPF2):​c.607G>A​(p.Val203Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,258 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: YIPF2 NM_001321439.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.31
• Publications: 1 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 2 ACMG points.

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

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.607G>A	p.Val203Met	missense	Exon 7 of 10	NP_001308368.1	Q9BWQ6
	YIPF2	NM_024029.5		c.607G>A	p.Val203Met	missense	Exon 7 of 10	NP_076934.1	Q9BWQ6
	YIPF2	NM_001321440.2		c.490G>A	p.Val164Met	missense	Exon 6 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.607G>A	p.Val203Met	missense	Exon 7 of 10	ENSP00000466055.1	Q9BWQ6
	YIPF2	ENST00000253031.6	TSL:1	c.607G>A	p.Val203Met	missense	Exon 7 of 10	ENSP00000253031.1	Q9BWQ6
	YIPF2	ENST00000874113.1		c.607G>A	p.Val203Met	missense	Exon 7 of 10	ENSP00000544172.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 247902 AF XY: 0.00000745

Gnomad AFR exome AF: 0.0000624

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461056 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 726806

African (AFR) AF: 0.0000897 AC: 3 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 86154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111648

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152202 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74350

African (AFR) AF: 0.0000483 AC: 2 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000875 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.064	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.10
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.3
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.26
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.067	T
Polyphen		0.99	D
Vest4		0.51
MVP		0.22
MPC		0.53
ClinPred		0.82	D
GERP RS		4.6
PromoterAI		-0.0022	Neutral
Varity_R		0.30
gMVP		0.64
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs778397143; hg19: chr19-11034553;