4-44650100-T-A

Position:

• chr4-44650100-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182592.3(YIPF7):​c.1A>T​(p.Met1?) variant causes a initiator codon, splice region change. The variant was absent in control chromosomes in GnomAD project. 2/3 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)
• Consequence: YIPF7 NM_182592.3 initiator_codon, splice_region
• Scores: Splicing: ADA: 0.9121
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.30

Genes affected

YIPF7 (HGNC:26825): (Yip1 domain family member 7) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport and vesicle fusion with Golgi apparatus. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. Predicted to be active in trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YIPF7	NM_182592.3	c.1A>T	p.Met1?	initiator_codon_variant, splice_region_variant	2/6	ENST00000415895.9	NP_872398.3
YIPF7	NM_001387382.1	c.1A>T	p.Met1?	initiator_codon_variant, splice_region_variant	2/3		NP_001374311.1
YIPF7	XM_047450094.1	c.136A>T	p.Met46Leu	missense_variant, splice_region_variant	2/7		XP_047306050.1
YIPF7	XM_011513679.3	c.73A>T	p.Met25Leu	missense_variant, splice_region_variant	2/7		XP_011511981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YIPF7	ENST00000415895.9	c.1A>T	p.Met1?	initiator_codon_variant, splice_region_variant	2/6	5	NM_182592.3	ENSP00000412696.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2024

The c.73A>T (p.M25L) alteration is located in exon 2 (coding exon 2) of the YIPF7 gene. This alteration results from a A to T substitution at nucleotide position 73, causing the methionine (M) at amino acid position 25 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.095	.;T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.90	D;T;D
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.51	D;T;D
MetaSVM	Benign	-0.32	T
MutationAssessor	Uncertain	2.7	.;M;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.3	.;N;.
REVEL	Benign	0.21
Sift	Benign	0.088	.;T;.
Sift4G	Benign	0.098	T;T;D
Polyphen		0.058	.;B;.
Vest4		0.92
MutPred		0.50		.;Gain of glycosylation at S26 (P = 0.0436);.;
MVP		0.24
MPC		0.015
ClinPred		0.70	D
GERP RS		5.5
Varity_R		0.27
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.91
dbscSNV1_RF	Pathogenic	0.84
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-44652117;