19-38307501-A-T

Position:

• chr19-38307501-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039672.3(YIF1B):​c.716T>A​(p.Met239Lys) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: YIF1B NM_001039672.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.863

Genes affected

YIF1B (HGNC:30511): (Yip1 interacting factor homolog B, membrane trafficking protein) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport; protein targeting to membrane; and sperm axoneme assembly. Located in Golgi apparatus; endoplasmic reticulum; and endoplasmic reticulum-Golgi intermediate compartment. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16504106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YIF1B	NM_001039672.3	c.716T>A	p.Met239Lys	missense_variant	7/8	ENST00000339413.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YIF1B	ENST00000339413.11	c.716T>A	p.Met239Lys	missense_variant	7/8	1	NM_001039672.3	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 24, 2020

The alteration results in an amino acid change:_x000D_ _x000D_ The c.716T>A (p.M239K) alteration is located in coding exon 7 of the YIF1B gene. This alteration results from a T to A substitution at nucleotide position 716, causing the methionine (M) at amino acid position 239 to be replaced by a lysine (K). The alteration is not observed in population databases:_x000D_ _x000D_ Based on data from the Genome Aggregation Database (gnomAD), the YIF1B c.716T>A alteration was not observed, with coverage at this position. The altered amino acid is not conserved throughout evolution:_x000D_ _x000D_ The p.M239 amino acid is not conserved in available vertebrate species. The alteration is predicted tolerated by in silico modeling:_x000D_ _x000D_ The p.M239K alteration is predicted to be tolerated by in silico analysis. 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	Pathogenic	0.78
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Benign	0.89
DEOGEN2	Benign	0.019	.;.;.;T;T;.;.;.;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.25	N
LIST_S2	Uncertain	0.89	D;D;.;D;D;D;.;D;T
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.17	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.69	.;.;.;N;.;.;.;.;.
MutationTaster	Benign	0.94	N;N;N;N;N;N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.0	.;N;N;N;.;N;.;.;.
REVEL	Uncertain	0.33
Sift	Benign	0.25	.;T;T;T;.;T;.;.;.
Sift4G	Benign	0.29	T;T;T;T;T;T;T;T;.
Polyphen		0.0040	B;B;B;B;.;.;B;B;.
Vest4		0.50
MutPred		0.48		.;.;.;Gain of catalytic residue at M239 (P = 0.0037);.;.;.;.;.;
MVP		0.59
MPC		0.63
ClinPred		0.30	T
GERP RS		1.8
Varity_R		0.13
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1969104515; hg19: chr19-38798141;