2-127702002-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BS1 BS2

The NM_032740.4(SFT2D3):​c.474C>T​(p.Phe158Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,322,452 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0056 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00050 (4 hom.)
• Consequence: SFT2D3 NM_032740.4 synonymous
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP7: Synonymous conserved (PhyloP=1.67 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00565 (851/150698) while in subpopulation AFR AF = 0.0196 (809/41378). AF 95% confidence interval is 0.0184. There are 2 homozygotes in GnomAd4. There are 418 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFT2D3	NM_032740.4	c.474C>T	p.Phe158Phe	synonymous_variant	Exon 1 of 1	ENST00000310981.6	NP_116129.3
WDR33	NM_018383.5	c.*4321G>A		3_prime_UTR_variant	Exon 22 of 22	ENST00000322313.9	NP_060853.3
WDR33	XM_011511436.2	c.*4321G>A		3_prime_UTR_variant	Exon 22 of 22		XP_011509738.1
WDR33	XM_005263697.4	c.*4491G>A		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>T	p.Phe158Phe	synonymous_variant	Exon 1 of 1	6	NM_032740.4	ENSP00000310803.3
WDR33	ENST00000322313.9	c.*4321G>A		3_prime_UTR_variant	Exon 22 of 22	1	NM_018383.5	ENSP00000325377.3

Frequencies

GnomAD3 genomes AF: 0.00566 AC: 852 AN: 150590 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00212

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: 0.0000296

Gnomad OTH AF: 0.00386

GnomAD2 exomes AF: 0.000662 AC: 6 AN: 9068 AF XY: 0.000340

Gnomad AFR exome AF: 0.0241

Gnomad AMR exome AF: 0.00212

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000501 AC: 587 AN: 1171754 Hom.: 4 Cov.: 31 AF XY: 0.000440 AC XY: 251 AN XY: 569876

African (AFR) AF: 0.0216 AC: 493 AN: 22794

American (AMR) AF: 0.00215 AC: 20 AN: 9298

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 25110

South Asian (SAS) AF: 0.0000204 AC: 1 AN: 48928

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

Middle Eastern (MID) AF: 0.000311 AC: 1 AN: 3218

European-Non Finnish (NFE) AF: 0.0000206 AC: 20 AN: 972058

Other (OTH) AF: 0.00111 AC: 52 AN: 46864

GnomAD4 genome AF: 0.00565 AC: 851 AN: 150698 Hom.: 2 Cov.: 33 AF XY: 0.00568 AC XY: 418 AN XY: 73624

African (AFR) AF: 0.0196 AC: 809 AN: 41378

American (AMR) AF: 0.00211 AC: 32 AN: 15146

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

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

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

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

European-Non Finnish (NFE) AF: 0.0000296 AC: 2 AN: 67480

Other (OTH) AF: 0.00382 AC: 8 AN: 2092

Alfa AF: 0.000210 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	7.8
DANN	Uncertain	0.98
PhyloP100		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs559933448; hg19: chr2-128459576;