6-43516856-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_015388.4(YIPF3):c.-49C>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 0.0209 in 1,548,304 control chromosomes in the GnomAD database, including 392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (33 hom., cov: 33)
  • Exomes 𝑓: 0.021 (359 hom.)
• Consequence: YIPF3 NM_015388.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0290

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=-0.81).
• BP6: Variant 6-43516856-G-A is Benign according to our data. Variant chr6-43516856-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1201016.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0163 (2488/152394) while in subpopulation NFE AF= 0.0262 (1786/68040). AF 95% confidence interval is 0.0252. There are 33 homozygotes in gnomad4. There are 1178 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YIPF3	NM_015388.4	c.-49C>T		5_prime_UTR_variant	1/9	ENST00000372422.7
YIPF3	XM_047418608.1	c.-480C>T		5_prime_UTR_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YIPF3	ENST00000372422.7	c.-49C>T		5_prime_UTR_variant	1/9	1	NM_015388.4	P2

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 2489 AN: 152276 Hom.: 33 Cov.: 33

Gnomad AFR AF: 0.00357

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.0248

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0263

Gnomad OTH AF: 0.0148

GnomAD3 exomes AF: 0.0149 AC: 2380 AN: 159786 Hom.: 26 AF XY: 0.0142 AC XY: 1210 AN XY: 85000

Gnomad AFR exome AF: 0.00284

Gnomad AMR exome AF: 0.00847

Gnomad ASJ exome AF: 0.00365

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00222

Gnomad FIN exome AF: 0.0262

Gnomad NFE exome AF: 0.0245

Gnomad OTH exome AF: 0.0195

GnomAD4 exome AF: 0.0214 AC: 29808 AN: 1395910 Hom.: 359 Cov.: 29 AF XY: 0.0207 AC XY: 14302 AN XY: 689360

Gnomad4 AFR exome AF: 0.00325

Gnomad4 AMR exome AF: 0.00881

Gnomad4 ASJ exome AF: 0.00410

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.00232

Gnomad4 FIN exome AF: 0.0273

Gnomad4 NFE exome AF: 0.0248

Gnomad4 OTH exome AF: 0.0176

GnomAD4 genome AF: 0.0163 AC: 2488 AN: 152394 Hom.: 33 Cov.: 33 AF XY: 0.0158 AC XY: 1178 AN XY: 74530

Gnomad4 AFR AF: 0.00356

Gnomad4 AMR AF: 0.0132

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00310

Gnomad4 FIN AF: 0.0248

Gnomad4 NFE AF: 0.0262

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00689 Hom.: 7

Bravo AF: 0.0143

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.2
Dann	Benign	0.87

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: rs2231762; hg19: chr6-43484594;