Genetic Variant YIPF3:p.Val335Phe (chr6-43512217-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015388.4(YIPF3):c.1003G>T(p.Val335Phe) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V335I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

YIPF3
NM_015388.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.206

Publications

0 publications found

Variant links:

Genes affected

YIPF3 (HGNC:21023): (Yip1 domain family member 3) Predicted to be involved in cell differentiation. Located in Golgi apparatus and transport vesicle. [provided by Alliance of Genome Resources, Apr 2022]

YIPF3 links:

POLR1C (HGNC:20194): (RNA polymerase I and III subunit C) The protein encoded by this gene is a subunit of both RNA polymerase I and RNA polymerase III complexes. The encoded protein is part of the Pol core element. Mutations in this gene have been associated with Treacher Collins syndrome (TCS) and hypomyelinating leukodystrophy 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

POLR1C Gene-Disease associations (from GenCC):

hypomyelinating leukodystrophy 11
Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Treacher Collins syndrome 3
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
Treacher-Collins syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

POLR1C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11303583).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015388.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YIPF3	NM_015388.4	MANE Select	c.1003G>T	p.Val335Phe	missense	Exon 9 of 9	NP_056203.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
YIPF3	ENST00000372422.7	TSL:1 MANE Select	c.1003G>T	p.Val335Phe	missense	Exon 9 of 9	ENSP00000361499.2	Q9GZM5
YIPF3	ENST00000940674.1		c.1102G>T	p.Val368Phe	missense	Exon 9 of 9	ENSP00000610733.1
YIPF3	ENST00000506469.5	TSL:5	c.1021G>T	p.Val341Phe	missense	Exon 9 of 9	ENSP00000425494.1	E7EQR8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.37

CADD

Benign

2.8

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.045

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.68

M_CAP

Benign

0.042

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

-0.21

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.26

REVEL

Benign

0.12

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.012

Polyphen

0.050

Vest4

0.31

MutPred

0.32

Gain of loop (P = 0.0166)

MVP

0.068

MPC

0.40

ClinPred

0.29

GERP RS

-0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.62

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over