1-53871408-C-T

Variant names:

• chr1-53871408-C-T
• NM_018982.5:c.445G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018982.5(YIPF1):​c.445G>A​(p.Glu149Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: YIPF1 NM_018982.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.543

Genes affected

YIPF1 (HGNC:25231): (Yip1 domain family member 1) Predicted to enable small GTPase binding activity. Predicted to be involved in vesicle-mediated transport. Located in several cellular components, including Golgi apparatus subcompartment; nucleoplasm; and transport vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05761701).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YIPF1	NM_018982.5	c.445G>A	p.Glu149Lys	missense_variant	Exon 7 of 11	ENST00000072644.7	NP_061855.1
YIPF1	NR_036639.2	n.799G>A		non_coding_transcript_exon_variant	Exon 7 of 12
YIPF1	NR_036640.2	n.579G>A		non_coding_transcript_exon_variant	Exon 6 of 11
YIPF1	NR_135075.2	n.499G>A		non_coding_transcript_exon_variant	Exon 5 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YIPF1	ENST00000072644.7	c.445G>A	p.Glu149Lys	missense_variant	Exon 7 of 11	1	NM_018982.5	ENSP00000072644.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.445G>A (p.E149K) alteration is located in exon 7 (coding exon 5) of the YIPF1 gene. This alteration results from a G to A substitution at nucleotide position 445, causing the glutamic acid (E) at amino acid position 149 to be replaced by a lysine (K). 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	0.085
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.4	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.071
Sift	Benign	0.35	T
Sift4G	Benign	0.50	T
Polyphen		0.0010	B
Vest4		0.21
MutPred		0.38		Gain of ubiquitination at E149 (P = 0.0311);
MVP		0.048
MPC		0.030
ClinPred		0.46	T
GERP RS		3.8
Varity_R		0.036
gMVP		0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-54337081;