19-38304861-C-T

Variant names:

• chr19-38304861-C-T
• rs754564247
• NM_033520.3:c.218C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033520.3(C19orf33):​c.218C>T​(p.Ser73Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 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. S73Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: C19orf33 NM_033520.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.674
• Publications: 0 publications found

Genes affected

C19orf33 (HGNC:16668): (chromosome 19 open reading frame 33) The protein encoded by this gene has been shown to be upregulated in SV40-immortalized fibroblasts as well as in endometrial carcinoma cells. The encoded protein is found primarily in the nucleus. This protein may play a role in placental development and diseases such as pre-eclampsia. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

YIF1B (HGNC:30511): (Yip1 interacting factor homolog B, membrane trafficking protein) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport; protein targeting to membrane; and sperm axoneme assembly. Located in Golgi apparatus; endoplasmic reticulum; and endoplasmic reticulum-Golgi intermediate compartment. [provided by Alliance of Genome Resources, Apr 2022]

YIF1B Gene-Disease associations (from GenCC):

• Kaya-Barakat-Masson syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000267748 (HGNC:):

ACMG classification

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=0.15216729).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033520.3. 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
	C19orf33	NM_033520.3	MANE Select	c.218C>T	p.Ser73Phe	missense	Exon 4 of 4	NP_277055.1
	YIF1B	NM_001039672.3	MANE Select	c.*491G>A		3_prime_UTR	Exon 8 of 8	NP_001034761.1	Q5BJH7-1
	YIF1B	NM_001039673.3		c.*491G>A		3_prime_UTR	Exon 8 of 8	NP_001034762.1	Q5BJH7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C19orf33	ENST00000301246.10	TSL:1 MANE Select	c.218C>T	p.Ser73Phe	missense	Exon 4 of 4	ENSP00000301246.4	Q9GZP8-1
	YIF1B	ENST00000339413.11	TSL:1 MANE Select	c.*491G>A		3_prime_UTR	Exon 8 of 8	ENSP00000343435.5	Q5BJH7-1
	ENSG00000267748	ENST00000591889.2	TSL:2	c.*19C>T		3_prime_UTR	Exon 6 of 6	ENSP00000468040.1	K7EQZ3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461488 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 727014

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111962

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	19
DANN	Benign	0.93
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.67
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.070
Sift	Uncertain	0.019	D
Sift4G	Benign	0.098	T
Vest4		0.37
MutPred		0.19		Gain of catalytic residue at S73 (P = 0.0054)
MVP		0.12
MPC		0.56
ClinPred		0.95	D
GERP RS		2.2
gMVP		0.014
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs754564247; hg19: chr19-38795501;