6-43516905-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015388.4(YIPF3):c.-98C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0383 in 1,383,732 control chromosomes in the GnomAD database, including 1,456 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.054 (329 hom., cov: 33)
  • Exomes 𝑓: 0.036 (1127 hom.)
• Consequence: YIPF3 NM_015388.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0140

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 6-43516905-G-A is Benign according to our data. Variant chr6-43516905-G-A is described in ClinVar as [Benign]. Clinvar id is 1281294.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YIPF3	NM_015388.4	c.-98C>T		5_prime_UTR_variant	1/9	ENST00000372422.7
YIPF3	XM_047418608.1	c.-529C>T		5_prime_UTR_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YIPF3	ENST00000372422.7	c.-98C>T		5_prime_UTR_variant	1/9	1	NM_015388.4	P2

Frequencies

GnomAD3 genomes AF: 0.0544 AC: 8276 AN: 152232 Hom.: 328 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0329

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.0364

Gnomad SAS AF: 0.0805

Gnomad FIN AF: 0.0382

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0303

Gnomad OTH AF: 0.0435

GnomAD4 exome AF: 0.0363 AC: 44726 AN: 1231382 Hom.: 1127 Cov.: 17 AF XY: 0.0376 AC XY: 23078 AN XY: 614452

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.0228

Gnomad4 ASJ exome AF: 0.0540

Gnomad4 EAS exome AF: 0.0335

Gnomad4 SAS exome AF: 0.0785

Gnomad4 FIN exome AF: 0.0365

Gnomad4 NFE exome AF: 0.0303

Gnomad4 OTH exome AF: 0.0409

GnomAD4 genome AF: 0.0544 AC: 8293 AN: 152350 Hom.: 329 Cov.: 33 AF XY: 0.0557 AC XY: 4146 AN XY: 74498

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0329

Gnomad4 ASJ AF: 0.0487

Gnomad4 EAS AF: 0.0364

Gnomad4 SAS AF: 0.0805

Gnomad4 FIN AF: 0.0382

Gnomad4 NFE AF: 0.0303

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0490 Hom.: 55

Bravo AF: 0.0560

Asia WGS AF: 0.0710 AC: 246 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	7.9
Dann	Benign	0.89

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: rs2231759; hg19: chr6-43484643;