chr19-38309259-T-G

Position:

• chr19-38309259-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_001039672.3(YIF1B):​c.367A>C​(p.Lys123Gln) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: YIF1B NM_001039672.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.54

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 Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.975
• PP5: Variant 19-38309259-T-G is Pathogenic according to our data. Variant chr19-38309259-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 988954.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YIF1B	NM_001039672.3	c.367A>C	p.Lys123Gln	missense_variant	3/8	ENST00000339413.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YIF1B	ENST00000339413.11	c.367A>C	p.Lys123Gln	missense_variant	3/8	1	NM_001039672.3	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Kaya-Barakat-Masson syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 17, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	28
DANN	Uncertain	0.99
Eigen	Pathogenic	0.77
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D;D;.;D;D;.;D;D;D
M_CAP	Pathogenic	0.38	D
MetaRNN	Pathogenic	0.97	D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.64	D
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.67	T
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;.;D
Polyphen		1.0	D;D;D;D;.;D;D;.;.
Vest4		0.96
MutPred		0.92		.;.;.;Loss of ubiquitination at K123 (P = 0.0255);.;.;.;.;.;
MVP		0.76
MPC		1.2
ClinPred		0.99	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.89
gMVP		0.85

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: rs1969205627; hg19: chr19-38799899;