2-127702021-A-G

Variant names:

• chr2-127702021-A-G
• rs764196475
• NM_032740.4:c.493A>G

Variant summary

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

The NM_032740.4(SFT2D3):​c.493A>G​(p.Ser165Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 1,296,444 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S165R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: SFT2D3 NM_032740.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.99
• 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.

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.493A>G	p.Ser165Gly	missense	Exon 1 of 1	NP_116129.3
	WDR33	NM_018383.5	MANE Select	c.*4302T>C		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.493A>G	p.Ser165Gly	missense	Exon 1 of 1	ENSP00000310803.3	Q587I9
	WDR33	ENST00000322313.9	TSL:1 MANE Select	c.*4302T>C		3_prime_UTR	Exon 22 of 22	ENSP00000325377.3	Q9C0J8-1

Frequencies

GnomAD3 genomes AF: 0.000160 AC: 24 AN: 150452 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000530

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: 0.000222

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000401 AC: 2 AN: 4992 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000919

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000187 AC: 214 AN: 1145992 Hom.: 0 Cov.: 31 AF XY: 0.000182 AC XY: 101 AN XY: 554934

African (AFR) AF: 0.00 AC: 0 AN: 22464

American (AMR) AF: 0.00 AC: 0 AN: 8510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14668

East Asian (EAS) AF: 0.00 AC: 0 AN: 24710

South Asian (SAS) AF: 0.0000233 AC: 1 AN: 42912

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26466

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3066

European-Non Finnish (NFE) AF: 0.000219 AC: 210 AN: 957674

Other (OTH) AF: 0.0000659 AC: 3 AN: 45522

GnomAD4 genome AF: 0.000160 AC: 24 AN: 150452 Hom.: 0 Cov.: 33 AF XY: 0.000150 AC XY: 11 AN XY: 73436

African (AFR) AF: 0.0000243 AC: 1 AN: 41232

American (AMR) AF: 0.000530 AC: 8 AN: 15096

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9934

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

European-Non Finnish (NFE) AF: 0.000222 AC: 15 AN: 67422

Other (OTH) AF: 0.00 AC: 0 AN: 2066

Alfa AF: 0.000356 Hom.: 0

Bravo AF: 0.000113

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	0.22
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.74	T
M_CAP	Pathogenic	0.88	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.56	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		3.0
PrimateAI	Pathogenic	0.94	D
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.014	D
Polyphen		0.89	P
Vest4		0.50
MutPred		0.67		Gain of methylation at R164 (P = 0.0405)
MVP		0.72
ClinPred		0.38	T
GERP RS		3.5
Varity_R		0.86
gMVP		0.62
Mutation Taster		=19/81	disease causing

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: rs764196475; hg19: chr2-128459595;