5-144162287-G-A

Position:

• chr5-144162287-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_030799.9(YIPF5):​c.542C>T​(p.Ala181Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: YIPF5 NM_030799.9 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.11

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 5-144162287-G-A is Pathogenic according to our data. Variant chr5-144162287-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 1064542.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YIPF5	NM_030799.9	c.542C>T	p.Ala181Val	missense_variant	5/6	ENST00000274496.10	NP_110426.4
YIPF5	NM_001024947.4	c.542C>T	p.Ala181Val	missense_variant	5/6		NP_001020118.1
YIPF5	NM_001271732.2	c.380C>T	p.Ala127Val	missense_variant	4/5		NP_001258661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YIPF5	ENST00000274496.10	c.542C>T	p.Ala181Val	missense_variant	5/6	1	NM_030799.9	ENSP00000274496	P1
YIPF5	ENST00000448443.6	c.542C>T	p.Ala181Val	missense_variant	5/6	1		ENSP00000397704	P1
YIPF5	ENST00000513112.5	c.380C>T	p.Ala127Val	missense_variant	4/5	1		ENSP00000425422
YIPF5	ENST00000519064.5	c.380C>T	p.Ala127Val	missense_variant	4/5	2		ENSP00000429777

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000740 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Microcephaly, epilepsy, and diabetes syndrome 2 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0097	T;T;.;T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	.;D;D;D
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.36	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	L;L;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.84	N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.32	T;T;T;T
Sift4G	Benign	0.47	T;T;T;T
Polyphen		0.011	B;B;.;.
Vest4		0.63
MVP		0.17
MPC		0.13
ClinPred		0.70	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.64		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.64		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1752071425; hg19: chr5-143541851;