rs559933448

Variant names:

• chr2-127702002-C-A
• rs559933448
• NM_032740.4:c.474C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-127702002-C-A
• chr2-127702002-C-G
• chr2-127702002-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032740.4(SFT2D3):​c.474C>A​(p.Phe158Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000907 in 1,322,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000094 (0 hom.)
• Consequence: SFT2D3 NM_032740.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• Publications: 0 publications found

Genes affected

SFT2D3 (HGNC:28767): (SFT2 domain containing 3) Predicted to be involved in protein transport and vesicle-mediated transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

WDR33 (HGNC:25651): (WD repeat domain 33) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene is highly expressed in testis and the protein is localized to the nucleus. This gene may play important roles in the mechanisms of cytodifferentiation and/or DNA recombination. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30199137).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFT2D3	NM_032740.4	c.474C>A	p.Phe158Leu	missense_variant	Exon 1 of 1	ENST00000310981.6	NP_116129.3
WDR33	NM_018383.5	c.*4321G>T		3_prime_UTR_variant	Exon 22 of 22	ENST00000322313.9	NP_060853.3
WDR33	XM_011511436.2	c.*4321G>T		3_prime_UTR_variant	Exon 22 of 22		XP_011509738.1
WDR33	XM_005263697.4	c.*4491G>T		3_prime_UTR_variant	Exon 21 of 21		XP_005263754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFT2D3	ENST00000310981.6	c.474C>A	p.Phe158Leu	missense_variant	Exon 1 of 1	6	NM_032740.4	ENSP00000310803.3
WDR33	ENST00000322313.9	c.*4321G>T		3_prime_UTR_variant	Exon 22 of 22	1	NM_018383.5	ENSP00000325377.3

Frequencies

GnomAD3 genomes AF: 0.00000664 AC: 1 AN: 150590 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: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000939 AC: 11 AN: 1171752 Hom.: 0 Cov.: 31 AF XY: 0.0000105 AC XY: 6 AN XY: 569876

African (AFR) AF: 0.00 AC: 0 AN: 22796

American (AMR) AF: 0.00 AC: 0 AN: 9298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15602

East Asian (EAS) AF: 0.0000796 AC: 2 AN: 25110

South Asian (SAS) AF: 0.000164 AC: 8 AN: 48926

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3218

European-Non Finnish (NFE) AF: 0.00000103 AC: 1 AN: 972056

Other (OTH) AF: 0.00 AC: 0 AN: 46864

GnomAD4 genome AF: 0.00000664 AC: 1 AN: 150590 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 73506

African (AFR) AF: 0.00 AC: 0 AN: 41260

American (AMR) AF: 0.00 AC: 0 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67490

Other (OTH) AF: 0.00 AC: 0 AN: 2070

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.7
PrimateAI	Pathogenic	0.94	D
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.060
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.035	D
Polyphen		0.046	B
Vest4		0.33
MutPred		0.67		Loss of catalytic residue at F158 (P = 0.1271);
MVP		0.29
ClinPred		0.99	D
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.40
gMVP		0.46
Mutation Taster		=50/50

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: rs559933448; hg19: chr2-128459576;