4-44629468-T-C

Position:

• chr4-44629468-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_182592.3(YIPF7):​c.361A>G​(p.Met121Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,446,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: YIPF7 NM_182592.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.00

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37714463).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YIPF7	NM_182592.3	c.361A>G	p.Met121Val	missense_variant	4/6	ENST00000415895.9	NP_872398.3
YIPF7	XM_047450094.1	c.610A>G	p.Met204Val	missense_variant	5/7		XP_047306050.1
YIPF7	XM_011513679.3	c.547A>G	p.Met183Val	missense_variant	5/7		XP_011511981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YIPF7	ENST00000415895.9	c.361A>G	p.Met121Val	missense_variant	4/6	5	NM_182592.3	ENSP00000412696.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000118 AC: 17 AN: 1446148 Hom.: 0 Cov.: 30 AF XY: 0.00000975 AC XY: 7 AN XY: 717756

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000234

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000768

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000118

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000166 AC: 2

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

Feb 05, 2024

The c.433A>G (p.M145V) alteration is located in exon 4 (coding exon 4) of the YIPF7 gene. This alteration results from a A to G substitution at nucleotide position 433, causing the methionine (M) at amino acid position 145 to be replaced by a valine (V). 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	0.17
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.031	.;T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.38	T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.6	.;M
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.5	.;N
REVEL	Benign	0.16
Sift	Benign	0.035	.;D
Sift4G	Uncertain	0.055	T;D
Polyphen		0.12	.;B
Vest4		0.53
MutPred		0.55		.;Gain of catalytic residue at M145 (P = 0.0256);
MVP		0.18
MPC		0.020
ClinPred		0.82	D
GERP RS		5.3
Varity_R		0.23
gMVP		0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs749625378; hg19: chr4-44631485;