6-43516794-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.14C>T(p.Ala5Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0337 in 1,578,858 control chromosomes in the GnomAD database, including 1,029 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.025 (66 hom., cov: 33)
  • Exomes 𝑓: 0.035 (963 hom.)
• Consequence: YIPF3 NM_015388.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.82

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 (MetaRNN=0.0029116273).
• BP6: Variant 6-43516794-G-A is Benign according to our data. Variant chr6-43516794-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1216052.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.025 (3816/152374) while in subpopulation NFE AF= 0.0396 (2697/68040). AF 95% confidence interval is 0.0384. There are 66 homozygotes in gnomad4. There are 1742 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 66 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YIPF3	NM_015388.4	c.14C>T	p.Ala5Val	missense_variant	1/9	ENST00000372422.7
YIPF3	XM_047418608.1	c.-418C>T		5_prime_UTR_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YIPF3	ENST00000372422.7	c.14C>T	p.Ala5Val	missense_variant	1/9	1	NM_015388.4	P2

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 3818 AN: 152256 Hom.: 66 Cov.: 33

Gnomad AFR AF: 0.00714

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0204

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0106

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0397

Gnomad OTH AF: 0.0344

GnomAD3 exomes AF: 0.0263 AC: 4959 AN: 188902 Hom.: 90 AF XY: 0.0271 AC XY: 2767 AN XY: 102076

Gnomad AFR exome AF: 0.00566

Gnomad AMR exome AF: 0.0118

Gnomad ASJ exome AF: 0.0314

Gnomad EAS exome AF: 0.0000748

Gnomad SAS exome AF: 0.0130

Gnomad FIN exome AF: 0.0265

Gnomad NFE exome AF: 0.0423

Gnomad OTH exome AF: 0.0242

GnomAD4 exome AF: 0.0346 AC: 49383 AN: 1426484 Hom.: 963 Cov.: 31 AF XY: 0.0344 AC XY: 24313 AN XY: 706644

Gnomad4 AFR exome AF: 0.00575

Gnomad4 AMR exome AF: 0.0132

Gnomad4 ASJ exome AF: 0.0315

Gnomad4 EAS exome AF: 0.000135

Gnomad4 SAS exome AF: 0.0141

Gnomad4 FIN exome AF: 0.0295

Gnomad4 NFE exome AF: 0.0396

Gnomad4 OTH exome AF: 0.0303

GnomAD4 genome AF: 0.0250 AC: 3816 AN: 152374 Hom.: 66 Cov.: 33 AF XY: 0.0234 AC XY: 1742 AN XY: 74502

Gnomad4 AFR AF: 0.00716

Gnomad4 AMR AF: 0.0204

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0106

Gnomad4 FIN AF: 0.0238

Gnomad4 NFE AF: 0.0396

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.0380 Hom.: 98

Bravo AF: 0.0234

TwinsUK AF: 0.0337 AC: 125

ALSPAC AF: 0.0423 AC: 163

ESP6500AA AF: 0.00714 AC: 31

ESP6500EA AF: 0.0354 AC: 300

ExAC AF: 0.0229 AC: 2720

Asia WGS AF: 0.00549 AC: 19 AN: 3478

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
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.032	T;T;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.67	T;T;T
MetaRNN	Benign	0.0029	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.14	N;N;N
REVEL	Benign	0.089
Sift	Benign	0.21	T;T;T
Sift4G	Benign	0.10	T;D;.
Polyphen		0.0	B;B;.
Vest4		0.23
MPC		0.20
ClinPred		0.016	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.066
gMVP		0.35

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: rs2231763; hg19: chr6-43484532; COSMIC: COSV58304271; COSMIC: COSV58304271;