rs1265948005

Variant names:

• chr5-144160557-C-T
• rs1265948005
• NM_030799.9:c.614G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-144160557-C-T
• chr5-144160557-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_030799.9(YIPF5):​c.614G>A​(p.Gly205Glu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: YIPF5 NM_030799.9 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.82
• Publications: 0 publications found

Genes affected

YIPF5 (HGNC:24877): (Yip1 domain family member 5) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport; regulation of ER to Golgi vesicle-mediated transport; and vesicle fusion with Golgi apparatus. Located in Golgi apparatus; endoplasmic reticulum; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

YIPF5 Gene-Disease associations (from GenCC):

• microcephaly, epilepsy, and diabetes syndrome 2

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• primary microcephaly-epilepsy-permanent neonatal diabetes syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.872

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030799.9. 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
	YIPF5	NM_030799.9	MANE Select	c.614G>A	p.Gly205Glu	missense splice_region	Exon 6 of 6	NP_110426.4
	YIPF5	NM_001024947.4		c.614G>A	p.Gly205Glu	missense splice_region	Exon 6 of 6	NP_001020118.1	Q969M3-1
	YIPF5	NM_001271732.2		c.452G>A	p.Gly151Glu	missense splice_region	Exon 5 of 5	NP_001258661.1	Q969M3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YIPF5	ENST00000274496.10	TSL:1 MANE Select	c.614G>A	p.Gly205Glu	missense splice_region	Exon 6 of 6	ENSP00000274496.5	Q969M3-1
	YIPF5	ENST00000448443.6	TSL:1	c.614G>A	p.Gly205Glu	missense splice_region	Exon 6 of 6	ENSP00000397704.2	Q969M3-1
	YIPF5	ENST00000513112.5	TSL:1	c.452G>A	p.Gly151Glu	missense splice_region	Exon 5 of 5	ENSP00000425422.1	Q969M3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000408 AC: 1 AN: 245368 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 6.86e-7 AC: 1 AN: 1457348 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724750

African (AFR) AF: 0.00 AC: 0 AN: 33188

American (AMR) AF: 0.00 AC: 0 AN: 44122

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25908

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85282

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110340

Other (OTH) AF: 0.00 AC: 0 AN: 60196

GnomAD4 genome Cov.: 32

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	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Pathogenic	0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-0.42	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		7.8
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.61
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.99	D
Vest4		0.87
MutPred		0.69		Loss of helix (P = 0.079)
MVP		0.55
MPC		0.33
ClinPred		0.98	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.91
gMVP		0.87
Mutation Taster		=21/79	disease causing

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: rs1265948005; hg19: chr5-143540121;