6-43512208-C-A

Variant names:

• chr6-43512208-C-A
• rs764341744
• NM_015388.4:c.1012G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015388.4(YIPF3):​c.1012G>T​(p.Ala338Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: YIPF3 NM_015388.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.696

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08266887).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YIPF3	NM_015388.4	c.1012G>T	p.Ala338Ser	missense_variant	Exon 9 of 9	ENST00000372422.7	NP_056203.2
YIPF3	XM_047418608.1	c.907G>T	p.Ala303Ser	missense_variant	Exon 9 of 9		XP_047274564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YIPF3	ENST00000372422.7	c.1012G>T	p.Ala338Ser	missense_variant	Exon 9 of 9	1	NM_015388.4	ENSP00000361499.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152130 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461850 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152130 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74298

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	8.9
DANN	Uncertain	0.98
DEOGEN2	Benign	0.051	T;T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.083	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.050	N;N
REVEL	Benign	0.042
Sift	Uncertain	0.021	D;D
Sift4G	Benign	0.064	T;T
Polyphen		0.0030	B;B
Vest4		0.15
MutPred		0.16		.;Gain of glycosylation at A344 (P = 0.0406);
MVP		0.082
MPC		0.19
ClinPred		0.16	T
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.053
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs764341744; hg19: chr6-43479946;