chr2-127702048-G-A

Variant names:

• chr2-127702048-G-A
• rs552193516
• NM_032740.4:c.520G>A

Variant summary

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

The NM_032740.4(SFT2D3):​c.520G>A​(p.Gly174Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000065 in 1,230,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: SFT2D3 NM_032740.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.00
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11743906).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032740.4. 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
	SFT2D3	NM_032740.4	MANE Select	c.520G>A	p.Gly174Ser	missense	Exon 1 of 1	NP_116129.3
	WDR33	NM_018383.5	MANE Select	c.*4275C>T		3_prime_UTR	Exon 22 of 22	NP_060853.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFT2D3	ENST00000310981.6	TSL:6 MANE Select	c.520G>A	p.Gly174Ser	missense	Exon 1 of 1	ENSP00000310803.3	Q587I9
	WDR33	ENST00000322313.9	TSL:1 MANE Select	c.*4275C>T		3_prime_UTR	Exon 22 of 22	ENSP00000325377.3	Q9C0J8-1

Frequencies

GnomAD3 genomes AF: 0.0000399 AC: 6 AN: 150372 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000662

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000185 AC: 2 AN: 1079760 Hom.: 0 Cov.: 31 AF XY: 0.00000387 AC XY: 2 AN XY: 516262

African (AFR) AF: 0.0000913 AC: 2 AN: 21900

American (AMR) AF: 0.00 AC: 0 AN: 8194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13192

East Asian (EAS) AF: 0.00 AC: 0 AN: 23778

South Asian (SAS) AF: 0.00 AC: 0 AN: 25194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2838

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 921050

Other (OTH) AF: 0.00 AC: 0 AN: 42214

GnomAD4 genome AF: 0.0000399 AC: 6 AN: 150480 Hom.: 0 Cov.: 33 AF XY: 0.0000544 AC XY: 4 AN XY: 73520

African (AFR) AF: 0.000121 AC: 5 AN: 41382

American (AMR) AF: 0.0000661 AC: 1 AN: 15132

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9880

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67348

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000567

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		3.0
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	0.82	N
REVEL	Benign	0.067
Sift	Benign	0.21	T
Sift4G	Benign	0.34	T
Polyphen		0.080	B
Vest4		0.12
MutPred		0.45		Gain of glycosylation at G174 (P = 0.0539)
MVP		0.59
ClinPred		0.58	D
GERP RS		0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.045
gMVP		0.44
Mutation Taster		=68/32	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: rs552193516; hg19: chr2-128459622;