chr19-10923916-C-T

Variant names:

• chr19-10923916-C-T
• rs760937357
• NM_001321439.2:c.568G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001321439.2(YIPF2):​c.568G>A​(p.Val190Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: YIPF2 NM_001321439.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.284
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049402684).

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.568G>A	p.Val190Ile	missense	Exon 7 of 10	NP_001308368.1	Q9BWQ6
	YIPF2	NM_024029.5		c.568G>A	p.Val190Ile	missense	Exon 7 of 10	NP_076934.1	Q9BWQ6
	YIPF2	NM_001321440.2		c.451G>A	p.Val151Ile	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.568G>A	p.Val190Ile	missense	Exon 7 of 10	ENSP00000466055.1	Q9BWQ6
	YIPF2	ENST00000253031.6	TSL:1	c.568G>A	p.Val190Ile	missense	Exon 7 of 10	ENSP00000253031.1	Q9BWQ6
	YIPF2	ENST00000874113.1		c.568G>A	p.Val190Ile	missense	Exon 7 of 10	ENSP00000544172.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152150 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000807 AC: 2 AN: 247684 AF XY: 0.00000745

Gnomad AFR exome AF: 0.000125

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461066 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726838

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000120 AC: 4 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53234

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111738

Other (OTH) AF: 0.00 AC: 0 AN: 60338

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0352202), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152150 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74318

African (AFR) AF: 0.0000965 AC: 4 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000189

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	0.069
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.2
DANN	Benign	0.96
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.28
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.039
Sift	Benign	0.28	T
Sift4G	Benign	0.18	T
Polyphen		0.90	P
Vest4		0.13
MVP		0.048
MPC		0.091
ClinPred		0.046	T
GERP RS		-2.2
PromoterAI		-0.0072	Neutral
Varity_R		0.031
gMVP		0.23
Mutation Taster		=94/6	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: rs760937357; hg19: chr19-11034592;